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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

New Insights into Cold Shock Proteins Effects in Human Cancer: Correlation with Susceptibility, Prognosis and Therapeutical Perspectives

Author(s): Giuseppe Mirabile, Chiara Campo, Roberta Ettari, M'Hammed Aguennouz, Caterina Musolino and Alessandro Allegra*

Volume 29, Issue 38, 2022

Published on: 02 August, 2022

Page: [5965 - 5978] Pages: 14

DOI: 10.2174/0929867329666220601142924

Price: $65


The microenvironment of the tumor cells is central to its phenotypic modification. One of the essential elements of this milieu is thermal regulation. An augment in local temperature has been reported to augment the tumor cell's responsiveness to chemoand radiation treatment. Cold shock proteins are RNA/DNA binding proteins identified by the existence of one or more cold shock domains. In humans, the best studied components of this group of proteins are called Y-box binding proteins, such as Y-box binding protein-1 (YB-1), but several other proteins have been recognized. Biological functions of these proteins extend from the control of transcription, translation and splicing to the regulation of exosomal RNA content. Several findings correlate an altered cold shock protein expression profile with tumor diseases. In this review we summarize the data for a causative participation of cold shock proteins in cancer onset and diffusion. Furthermore, the possible use of cold shock proteins for diagnostics, prognosis, and as targets for cancer treatment is exposed.

Keywords: Cold shock protein, cancer, tumoral microenvironment, thermal stress, prognosis, microRNA.

Guan, K.; Nayernia, K.; Maier, L.S.; Wagner, S.; Dressel, R.; Lee, J.H.; Nolte, J.; Wolf, F.; Li, M.; Engel, W.; Hasenfuss, G. Pluripotency of spermatogonial stem cells from adult mouse testis. Nature, 2006, 440, 1199-1203.
Dewhirst, M.W.; Vujaskovic, Z.; Jones, E.; Thrall, D. Re-setting the biologic rationale for thermal therapy. Int. J. Hyperthermia, 2005, 21, 779-790.
Shamovsky, I.; Nudler, E. New insights into the mechanism of heat shock response activation. Cell. Mol. Life Sci., 2008, 65, 855-861.
Jones, P.G.; Inouye, M. The cold-shock response--a hot topic. Mol. Microbiol., 1994, 11(5), 811-818.
Gottesman, S. Chilled in translation: adapting to bacterial climate change. Mol. Cell, 2018, 70(2), 193-194.
Graumann, P.L.; Marahiel, M.A. A superfamily of proteins that contain the cold shock domain. Trends Biochem. Sci., 1998, 23(8), 286-290.
Brandt, S.; Raffetseder, U.; Djudjaj, S.; Schreiter, A.; Kadereit, B.; Michele, M.; Pabst, M.; Zhu, C.; Mertens, P.R. Cold shock Y-box protein-1 participates in signaling circuits with auto-regulatory activities. Eur. J. Cell Biol., 2011, 91(6-7), 464-471.
Lasham, A.; Print, C.G.; Woolley, A.G.; Dunn, S.E.; Braithwaite, A.W. YB-1: oncoprotein, prognostic marker and therapeutic target? Biochem. J., 2013, 449(1), 11-23.
Keto-Timonen, R.; Hietala, N.; Palonen, E.; Hakakorpi, A.; Lindström, M.; Korkeala, H. Cold Shock Proteins: A Minireview with Special Emphasis on Csp-family of Enteropathogenic Yersinia. Front. Microbiol., 2016, 7, 1151.
Ambros, V. A hierarchy of regulatory genes controls a larva-to-adult developmental switch in C. elegans. Cell, 1989, 57(1), 49-57.
Snyder, E.; Soundararajan, R.; Sharma, M.; Dearth, A.; Smith, B.; Braun, R.E. Compound heterozygosity for Y box proteins causes sterility due to loss of translational repression. PLoS Genet., 2015, 11(12), e1005690.
Berghella, L.; De Angelis, L.; De Buysscher, T.; Mortazavi, A.; Biressi, S.; Forcales, S.V.; Sirabella, D.; Cossu, G.; Wold, B.J. A highly conserved molecular switch binds MSY-3 to regulate myogenin repression in postnatal muscle. Genes Dev., 2008, 22(15), 2125-2138.
Lima, W.R.; Parreira, K.S.; Devuyst, O.; Caplanusi, A.; N’Kuli, F.; Marien, B.; Van Der Smissen, P.; Alves, P.M.; Verroust, P.; Christensen, E.I.; Terzi, F.; Matter, K.; Balda, M.S.; Pierreux, C.E.; Courtoy, P.J. ZONAB promotes proliferation and represses differentiation of proximal tubule epithelial cells. J. Am. Soc. Nephrol., 2010, 21(3), 478-488.
Hasegawa, S.L.; Doetsch, P.W.; Hamilton, K.K.; Martin, A.M.; Okenquist, S.A.; Lenz, J.; Boss, J.M. DNA binding properties of YB-1 and dbpA: binding to doublestranded, single-stranded, and abasic site containing DNAs. Nucleic Acids Res., 1991, 19(18), 4915-4920.
Zhu, C.; Sauter, E.; Schreiter, A.; van Roeyen, C.R.; Ostendorf, T.; Floege, J.; Gembardt, F.; Hugo, C.P.; Isermann, B.; Lindquist, J.A.; Mertens, P.R. Cold shock proteins mediate GN with Mesangio proliferation. J. Am. Soc. Nephrol., 2016, 27(12), 3678-3689.
Groblewski, G.E.; Yoshida, M.; Bragado, M.J.; Ernst, S.A.; Leykam, J.; Williams, J.A. Purification and characterization of a novel physiological substrate for calcineurin in mammalian cells. J. Biol. Chem., 1998, 273(35), 22738-22744.
Schafer, C.; Steffen, H.; Krzykowski, K.J.; Goke, B.; Groblewski, G.E. CRHSP-24 phosphorylation is regulated by multiple signaling pathways in pancreatic acinar cells. Am. J. Physiol. Gastrointest. Liver Physiol., 2003, 285(4), G726-G734.
Pfeiffer, J.R.; McAvoy, B.L.; Fecteau, R.E.; Deleault, K.M.; Brooks, S.A. CARHSP1 is required for effective tumor necrosis factor alpha mRNA stabilization and localizes to processing bodies and exosomes. Mol. Cell. Biol., 2011, 31(2), 277-286.
Anderson, E.C.; Catnaigh, P.O. Regulation of the expression and activity of Unr in mammalian cells. Biochem. Soc. Trans., 2015, 43(6), 1241-1246.
Ray, S.; Catnaigh, P.O.; Anderson, E.C. Post-transcriptional regulation of gene expression by Unr. Biochem. Soc. Trans., 2015, 43(3), 323-327.
Boussadia, O.; Amiot, F.; Cases, S.; Triqueneaux, G.; Jacquemin-Sablon, H.; Dautry, F. Transcription of unr (upstream of N-ras) down-modulates N-ras expression in-vivo. FEBS Lett., 1997, 420(1), 20-24.
Jacquemin-Sablon, H.; Triqueneaux, G.; Deschamps, S.; le Maire, M.; Doniger, J.; Dautry, F. Nucleic acid binding and intracellular localization of unr, a protein with five cold shock domains. Nucleic Acids Res., 1994, 22(13), 2643-2650.
Frye, B.C.; Halfter, S.; Djudjaj, S.; Muehlenberg, P.; Weber, S.; Raffetseder, U.; En-Nia, A.; Knott, H.; Baron, J.M.; Dooley, S. Y-box protein-1 is actively secreted through a non-classical pathway and acts as an extracellular mitogen. EMBO Rep., 2009, 10(7), 783-789.
Tacke, F.; Kanig, N.; En-Nia, A.; Kaehne, T.; Eberhardt, C.S.; Shpacovitch, V.; Trautwein, C.; Mertens, P.R. Y-box protein-1/p18 fragment identifies malignancies in patients with chronic liver disease. BMC Cancer, 2011, 11, 185.
Gulow, K.; Bienert, D.; Haas, I.G. BiP is feed-back regulated by control of protein translation efficiency. J. Cell Sci., 2002, 115(Pt 11), 2443-2452.
Allegra, A.; Sant’antonio, E.; Penna, G.; Alonci, A.; D’Angelo, A.; Russo, S.; Cannavò, A.; Gerace, D.; Musolino, C. Novel therapeutic strategies in multiple myeloma: role of the heat shock protein inhibitors. Eur. J. Haematol., 2011, 86(2), 93-110.
Murdaca, G.; Allegra, A.; Paladin, F.; Calapai, F.; Musolino, C.; Gangemi, S. Involvement of alarmins in the pathogenesis and progression of multiple myeloma. Int. J. Mol. Sci., 2021, 22(16), 9039.
[ 10.3390/ijms22169039]
Bernhardt, A.; Fehr, A.; Brandt, S.; Jerchel, S.; Ballhause, T.M.; Philipsen, L.; Stolze, S.; Geffers, R.; Wenig, H.; Fischer, K.D. Inflammatory cell infiltration and resolution of kidney inflammation is orchestrated by the cold-shock protein Y-box binding protein-1. Kidney Int., 2017, 92, 1157-1177.
Evdokimova, V.; Ruzanov, P.; Anglesio, M.S.; Sorokin, A.V.; Ovchinnikov, L.P.; Buckley, J.; Triche, T.J.; Sonenberg, N.; Sorensen, P.H. Akt-mediated YB-1 phosphorylation activates translation of silent mRNA species. Mol. Cell. Biol., 2006, 26(1), 277-292.
Kohno, K.; Izumi, H.; Uchiumi, T.; Ashizuka, M.; Kuwano, M. The pleiotropic functions of the Y-box-binding protein, YB-1. BioEssays, 2003, 25(7), 691-698.
Harada, M.; Hu, B.; Lu, J.; Wang, J.; Rinke, A.E.; Wu, Z.; Liu, T.; Phan, S.H. The dual distinct role of telomerase in repression of senescence and myofibroblast differentiation. Aging (Albany NY), 2021, 13(13), 16957-16973.
[ 10.18632/aging.203246]
Basaki, Y.; Hosoi, F.; Oda, Y.; Fotovati, A.; Maruyama, Y.; Oie, S.; Ono, M.; Izumi, H.; Kohno, K.; Sakai, K.; Shimoyama, T.; Nishio, K.; Kuwano, M. Akt dependent nuclear localization of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells. Oncogene, 2007, 26(19), 2736-2746.
En-Nia, A.; Yilmaz, E.; Klinge, U.; Lovett, D.H.; Stefanidis, I.; Mertens, P.R. Transcription factor YB-1 mediates DNA polymerase alpha gene expression. J. Biol. Chem., 2005, 280(9), 7702-7711.
Schittek, B.; Psenner, K.; Sauer, B.; Meier, F.; Iftner, T.; Garbe, C. The increased expression of Y box-binding protein 1 in melanoma stimulates proliferation and tumor invasion, antagonizes apoptosis and enhances chemoresistance. Int. J. Cancer, 2007, 120(10), 2110-2118.
Yoshimatsu, T.; Uramoto, H.; Oyama, T.; Yashima, Y.; Gu, C.; Morita, M.; Sugio, K.; Kohno, K.; Yasumoto, K. Y-box-binding protein-1 expression is not correlated with p53 expression but with proliferating cell nuclear antigen expression in non-small cell lung cancer. Anticancer Res., 2005, 25(5), 3437-3443.
Fan, L.; Jones, S.N.; Padden, C.; Shen, Q.; Newburger, P.E. Nuclease sensitive element binding protein 1 gene disruption results in early embryonic lethality. J. Cell. Biochem., 2006, 99(1), 140-145.
Lu, Z.H.; Books, J.T.; Ley, T.J. Cold shock domain family members YB-1 and MSY4 share essential functions during murine embryogenesis. Mol. Cell. Biol., 2006, 26(22), 8410-8417.
Yu, J.; Vodyanik, M.A.; Smuga-Otto, K.; Antosiewicz-Bourget, J.; Frane, J.L.; Tian, S.; Nie, J.; Jonsdottir, G.A.; Ruotti, V.; Stewart, R.; Slukvin, I.I.; Thomson, J.A. Induced pluripotent stem cell lines derived from human somatic cells. Science, 2007, 318(5858), 1917-1920.
Bargou, R.C.; Jurchott, K.; Wagener, C.; Bergmann, S.; Metzner, S.; Bommert, K.; Mapara, M.Y.; Winzer, K.J.; Dietel, M.; Dorken, B. Nuclear localization and increased levels of transcription factor YB-1 in primary human breast cancers are associated with intrinsic MDR1 gene expression. Nat. Med., 1997, 3(4), 447-450.
Bergmann, S.; Royer-Pokora, B.; Fietze, E.; Jurchott, K.; Hildebrandt, B.; Trost, D.; Leenders, F.; Claude, J.C.; Theuring, F.; Bargou, R. YB-1 provokes breast cancer through the induction of chromosomal instability that emerges from mitotic failure and centrosome amplification. Cancer Res., 2005, 65(10), 4078-4087.
Bommert, K.S.; Effenberger, M.; Leich, E.; Kuspert, M.; Murphy, D.; Langer, C.; Moll, R.; Janz, S.; Mottok, A.; Weissbach, S. The feed-forward loop between YB-1 and MYC is essential for multiple myeloma cell survival. Leukemia, 2012, 27(2), 441-450.
Sinnberg, T.; Sauer, B.; Holm, P.; Spangler, B.; Kuphal, S.; Bosserhoff, A.; Schittek, B. MAPK and PI3K/AKT mediated YB-1 activation promotes melanoma cell proliferation which is counteracted by an autoregulatory loop. Exp. Dermatol., 2012, 21(4), 265-270.
Kosnopfel, C.; Sinnberg, T.; Schittek, B. Y-box binding protein 1--a prognostic marker and target in tumour therapy. Eur. J. Cell Biol., 2014, 93(1-2), 61-70.
Chattopadhyay, R.; Das, S.; Maiti, A.K.; Boldogh, I.; Xie, J.; Hazra, T.K.; Kohno, K.; Mitra, S.; Bhakat, K.K. Regulatory role of human AP-endonuclease (APE1/Ref-1) in YB-1-mediated activation of the multidrug resistance gene MDR1. Mol. Cell. Biol., 2008, 28(23), 7066-7080.
Kuwano, M.; Oda, Y.; Izumi, H.; Yang, S.J.; Uchiumi, T.; Iwamoto, Y.; Toi, M.; Fujii, T.; Yamana, H.; Kinoshita, H. The role of nuclear Y-box binding protein 1 as a global marker in drug resistance. Mol. Cancer Ther., 2004, 3(11), 1485-1492.
Shen, H.; Xu, W.; Luo, W.; Zhou, L.; Yong, W.; Chen, F.; Wu, C.; Chen, Q.; Han, X. Upregulation of mdr1 gene is related to activation of the MAPK/ERK signal transduction pathway and YB-1 nuclear translocation in B-cell lymphoma. Exp. Hematol., 2011, 39(5), 558-569.
Setoguchi, K.; Cui, L.; Hachisuka, N.; Obchoei, S.; Shinkai, K.; Hyodo, F.; Kato, K.; Wada, F.; Yamamoto, T.; Harada-Shiba, M.; Obika, S.; Nakano, K. Antisense oligonucleotides targeting Y-box binding Protein-1 inhibit tumor angiogenesis by downregulating Bcl-xL-VEGFR2/-tie axes. Mol. Ther. Nucleic Acids, 2017, 9, 170-181.
Miao, X.; Wu, Y.; Wang, Y.; Zhu, X.; Yin, H.; He, Y.; Li, C.; Liu, Y.; Lu, X.; Chen, Y. Y-box-binding protein-1 (yb-1) promotes cell proliferation, adhesion and drug resistance in diffuse large b-cell lymphoma. Exp. Cell Res., 2016, 346, 157-166.
Guo, T.; Zhao, S.; Wang, P.; Xue, X.; Zhang, Y.; Yang, M.; Li, N.; Li, Z.; Xu, L.; Jiang, L. Yb-1 regulates tumor growth by promoting macc1/c-met pathway in human lung adenocarcinoma. Oncotarget, 2017, 8, 48110.
Wang, H.; Sun, R.; Chi, Z.; Li, S.; Hao, L. Silencing of y-box binding protein-1 by rna interference inhibits proliferation, invasion, and metastasis, and enhances sensitivity to cisplatin through nf-kB signaling pathway in human neuroblastoma sh-sy5y cells. Mol. Cell. Biochem., 2017, 433, 1-12.
Chao, H-M.; Huang, H-X.; Chang, P-H.; Tseng, K-C.; Miyajima, A.; Chern, E. Y-box binding protein-1 promotes hepatocellular carcinoma-initiating cell progression and tumorigenesis via Wnt/β-catenin pathway. Oncotarget, 2017, 8, 2604.
Gong, H.; Gao, S.; Yu, C.; Li, M.; Liu, P.; Zhang, G.; Song, J.; Zheng, J. Effect and mechanism of yb-1 knockdown on glioma cell growth, migration, and apoptosis. Acta Biochim. Biophys. Sin. (Shanghai), 2020, 52, 168-179.
Wang, Y.; Wang, Y.; Xu, L.; Lu, X.; Fu, D.; Su, J.; Geng, H.; Qin, G.; Chen, R.; Quan, C. Cd4+ t cells promote renal cell carcinoma proliferation via modulating ybx1. Exp. Cell Res., 2018, 363, 95-101.
Johnson, T.G.; Schelch, K.; Mehta, S.; Burgess, A.; Reid, G. Why be one protein when you can affect many? The multiple roles of yb-1 in lung cancer and mesothelioma. Front. Cell Dev. Biol., 2019, 7, 221.
Lim, W.K.; Lyashenko, E.; Califano, A. Master regulators used as breast cancer metastasis classifier. Pac. Symp. Biocomput., 2009, 504-515.
Homer, C.; Knight, D.A.; Hananeia, L.; Sheard, P.; Risk, J.; Lasham, A.; Royds, J.A.; Braithwaite, A.W. Y-box factor yb1 controls p53 apoptotic function. Oncogene, 2005, 24, 8314-8325.
Davies, A.H.; Barrett, I.; Pambid, M.R.; Hu, K.; Stratford, A.L.; Freeman, S.; Berquin, I.M.; Pelech, S.; Hieter, P.; Maxwell, C. Yb-1 evokes susceptibility to cancer through cytokinesis failure, mitotic dysfunction and her2 amplification. Oncogene, 2011, 30, 3649-3660.
Lasham, A.; Mehta, S.Y.; Fitzgerald, S.J.; Woolley, A.G.; Hearn, J.I.; Hurley, D.G.; Ruza, I.; Algie, M.; Shelling, A.N.; Braithwaite, A.W. A novel egr-1 dependent mechanism for yb-1 modulation of paclitaxel response in a triple negative breast cancer cell line. Int. J. Cancer, 2016, 139, 1157-1170.
Tong, H.; Zhao, K.; Zhang, J.; Zhu, J.; Xiao, J. Yb-1 modulates the drug resistance of glioma cells by activation of mdm2/p53 pathway. Drug Des. Devel. Ther., 2019, 13, 317.
Jürchott, K.; Bergmann, S.; Stein, U.; Walther, W.; Janz, M.; Manni, I.; Piaggio, G.; Fietze, E.; Dietel, M.; Royer, H-D. Yb-1 as a cell cycle regulated transcription factor facilitating cyclin a and cyclin b1 gene expression. J. Biol. Chem., 2003, 278(30), 27988-27996.
Basaki, Y.; Taguchi, K-I.; Izumi, H.; Murakami, Y.; Kubo, T.; Hosoi, F.; Watari, K.; Nakano, K.; Kawaguchi, H.; Ohno, S. Y-box binding protein-1 (yb-1) promotes cell cycle progression through cdc6-dependent pathway in human cancer cells. Eur. J. Cancer, 2010, 46, 954-965.
Khandelwal, P.; Padala, M.K.; Cox, J.; Guntaka, R.V. The terminal domain of y-box binding protiens-1 induces cell cycle arrest in g2/m phase by binding to cyclin d1. Int. J. Cell. Biol., 2009, 2009, 243532.
Guarino, A.M.; Troiano, A.; Pizzo, E.; Bosso, A.; Vivo, M.; Pinto, G.; Amoresano, A.; Pollice, A.; La Mantia, G.; Calabrò, V. Oxidative stress causes enhanced secretion of yb-1 protein that restrains proliferation of receiving cells. Genes (Basel), 2018, 9, 513.
Kotake, Y.; Arikawa, N.; Tahara, K.; Maru, H.; Naemura, M. Y-box binding protein 1 is involved in regulating the g2/m phase of the cell cycle. Anticancer Res., 2017, 37, 1603-1608.
Sutherland, B.W.; Kucab, J.; Wu, J.; Lee, C.; Cheang, M.C.; Yorida, E.; Turbin, D.; Dedhar, S.; Nelson, C.; Pollak, M.; Leighton Grimes, H.; Miller, K.; Badve, S.; Huntsman, D.; Blake-Gilks, C.; Chen, M.; Pallen, C.J.; Dunn, S.E. Akt phosphorylates the Y-box binding protein 1 at Ser102 located in the cold shock domain and affects the anchorage independent growth of breast cancer cells. Oncogene, 2005, 24(26), 4281-4292.
Das, S.; Chattopadhyay, R.; Bhakat, K.K.; Boldogh, I.; Kohno, K.; Prasad, R.; Wilson, S.H.; Hazra, T.K. Stimulation of NEIL2-mediated oxidized base excision repair via YB-1 interaction during oxidative stress. J. Biol. Chem., 2007, 282(39), 28474-28484.
Evdokimova, V.; Ovchinnikov, L.P.; Sorensen, P.H. Y-box binding protein 1: providing a new angle on translational regulation. Cell Cycle, 2006, 5(11), 1143-1147.
Evdokimova, V.; Ruzanov, P.; Imataka, H.; Raught, B.; Svitkin, Y.; Ovchinnikov, L.P.; Sonenberg, N. The major mRNA-associated protein YB-1 is a potent 5′ cap-dependent mRNA stabilizer. EMBO J., 2001, 20(19), 5491-5502.
Shiota, M.; Izumi, H.; Onitsuka, T.; Miyamoto, N.; Kashiwagi, E.; Kidani, A.; Yokomizo, A.; Naito, S.; Kohno, K. Twist promotes tumor cell growth through YB-1 expression. Cancer Res., 2008, 68(1), 98-105.
Tiwari, A.; Rebholz, S.; Maier, E.; Dehghan Harati, M.; Zips, D.; Sers, C.; Rodemann, H.P.; Toulany, M. Stress-Induced Phosphorylation of Nuclear YB-1 Depends on Nuclear Trafficking of p90 Ribosomal S6 Kinase. Int. J. Mol. Sci., 2018, 19(8), 2441.
Lasham, A.; Moloney, S.; Hale, T.; Homer, C.; Zhang, Y.F.; Murison, J.G.; Braithwaite, A.W.; Watson, J. The Y-box-binding protein, YB1, is a potential negative regulator of the p53 tumor suppressor. J. Biol. Chem., 2003, 278(37), 35516-35523.
Kashihara, M.; Azuma, K.; Kawahara, A.; Basaki, Y.; Hattori, S.; Yanagawa, T.; Terazaki, Y.; Takamori, S.; Shirouzu, K.; Aizawa, H. Nuclear Ybox binding protein-1, a predictive marker of prognosis, is correlated with expression of HER2/ErbB2 and HER3/ErbB3 in non-small cell lung cancer. J. Thorac. Oncol., 2009, 4, 1066-1074.
Hyogotani, A.; Ito, K.; Yoshida, K.; Izumi, H.; Kohno, K.; Amamo, J. Association of nuclear YB- 1 localization with lung resistance-related protein and epidermal growth factor receptor expression in lung cancer. Clin. Lung Cancer, 2012, 13, 375-384.
Shibata, T.; Kan, H.; Murakami, Y.; Ureshino, H.; Watari, K.; Kawahara, A.; Kage, M.; Hattori, S.; Ono, M.; Kuwano, M. Y-box binding protein-1 contributes to both HER2/ErbB2 expression and lapatinib sensitivity in human gastric cancer cells. Mol. Cancer Ther., 2013, 12, 737-746.
Wu, J.; Lee, C.; Yokom, D.; Jiang, H.; Cheang, M.C.; Yorida, E.; Turbin, D.; Berquin, I.M.; Mertens, P.R.; Iftner, T. Disruption of the Y-box binding protein-1 results in suppression of the epidermal growth factor receptor and HER-2. Cancer Res., 2006, 66, 4872-4879.
Fujii, T.; Kawahara, A.; Basaki, Y.; Hattori, S.; Nakashima, K.; Nakano, K.; Shirouzu, K.; Kohno, K.; Yanagawa, T.; Yamana, H. Expression of HER2 and estrogen receptor alpha depends upon nuclear localization of Y-box binding protein-1 in human breast cancers. Cancer Res., 2008, 68, 1504-1512.
Nishio, S.; Ushijima, K.; Yamaguchi, T.; Sasajima, Y.; Tsuda, H.; Kasamatsu, T.; Kage, M.; Ono, M.; Kuwano, M.; Kamura, T. Nuclear Y-box-binding protein-1 is a poor prognostic marker and related to epidermal growth factor receptor in uterine cervical cancer. Gynecol. Oncol., 2014, 132(3), 703-708.
Berquin, I.M.; Pang, B.; Dziubinski, M.L.; Scott, L.M.; Chen, Y.Q.; Nolan, G.P.; Ethier, S.P. Y-box-binding protein 1 confers EGF independence to human mammary epithelial cells. Oncogene, 2005, 24(19), 3177-3186.
Sakura, H.; Maekawa, T.; Imamoto, F.; Yasuda, K.; Ishii, S. Two human genes isolated by a novel method encode DNA-binding proteins containing a common region of homology. Gene, 1988, 73(2), 499-507.
Huo, M.; Yu, K.; Zheng, Y.; Liu, L.; Zhao, H.; Li, X.; Huang, C.; Zhang, J. Integrated bioinformatics analysis revealed the regulation of angiogenesis by tumor cells in hepatocellular carcinoma. Biosci. Rep., 2021, 41(7)
Quartarone, E.; Alonci, A.; Allegra, A.; Bellomo, G.; Calabrò, L.; D’Angelo, A.; Del Fabro, V.; Grasso, A.; Cincotta, M.; Musolino, C. Differential levels of soluble angiopoietin-2 and Tie-2 in patients with haematological malignancies. Eur. J. Haematol., 2006, 77(6), 480-485.
Takahashi, M.; Shimajiri, S.; Izumi, H.; Hirano, G.; Kashiwagi, E.; Yasuniwa, Y.; Wu, Y.; Han, B.; Akiyama, M.; Nishizawa, S.; Sasaguri, Y.; Kohno, K. Y-box binding protein-1 is a novel molecular target for tumor vessels. Cancer Sci., 2010, 101(6), 1367-1373.
[ 10.1111/j.1349-7006.2010.01534.x]
Musolino, C.; Allegra, A.; Saija, A.; Alonci, A.; Russo, S.; Spatari, G.; Penna, G.; Gerace, D.; Cristani, M.; David, A.; Saitta, S.; Gangemi, S. Changes in advanced oxidation protein products, advanced glycation end products, and s-nitrosylated proteins, in patients affected by polycythemia vera and essential thrombocythemia. Clin. Biochem., 2012, 45(16-17), 1439-1443.
Allegra, A.; Speciale, A.; Molonia, M.S.; Guglielmo, L.; Musolino, C.; Ferlazzo, G.; Costa, G.; Saija, A.; Cimino, F. Curcumin ameliorates the in-vitro efficacy of carfilzomib in human multiple myeloma U266 cells targeting p53 and NF-κB pathways. Toxicol. in-vitro, 2018, 47, 186-194.
Imbesi, S.; Musolino, C.; Allegra, A.; Saija, A.; Morabito, F.; Calapai, G.; Gangemi, S. Oxidative stress in oncohematologic diseases: an update. Expert Rev. Hematol., 2013, 6(3), 317-325.
Obulhasim, G.; Yasen, M.; Kajino, K.; Mogushi, K.; Tanaka, S.; Mizushima, H.; Tanaka, H.; Arii, S.; Hino, O. Up-regulation of dbpA mRNA in hepatocellular carcinoma associated with metabolic syndrome. Hepatol. Int., 2013, 7(1), 215-225.
Tang, C.; Wang, Y.; Lan, D.; Feng, X.; Zhu, X.; Nie, P.; Yue, H. Analysis of gene expression profiles reveals the regulatory network of cold-inducible RNA-binding protein mediating the growth of BHK-21 cells. Cell Biol. Int., 2015, 39(6), 678-689.
Jiang, S.; Baltimore, D. RNA-binding protein Lin28 in cancer and immunity. Cancer Lett., 2016, 375(1), 108-113.
Evans, J.R.; Mitchell, S.A.; Spriggs, K.A.; Ostrowski, J.; Bomsztyk, K.; Ostarek, D.; Willis, A.E. Members of the poly (rC) binding protein family stimulate the activity of the c-myc internal ribosome entry segment in-vitro and in-vivo. Oncogene, 2003, 22(39), 8012-8020.
Grosset, C.; Chen, C.Y.; Xu, N.; Sonenberg, N.; Jacquemin-Sablon, H.; Shyu, A.B. A mechanism for translationally coupled mRNA turnover: interaction between the poly(a) tail and a c-fos RNA coding determinant via a protein complex. Cell, 2000, 103(1), 29-40.
Wurth, L.; Papasaikas, P.; Olmeda, D.; Bley, N.; Calvo, G.T.; Guerrero, S.; Cerezo-Wallis, D.; Martinez-Useros, J.; Garcia-Fernandez, M.; Huttelmaier, S.; Soengas, M.S.; Gebauer, F. UNR/CSDE1 drives a post-transcriptional program to promote melanoma invasion and metastasis. Cancer Cell, 2016, 30(5), 694-707.
Evdokimova, V.; Tognon, C.; Ng, T.; Ruzanov, P.; Melnyk, N.; Fink, D.; Sorokin, A.; Ovchinnikov, L.P.; Davicioni, E.; Triche, T.J.; Sorensen, P.H. Translational activation of snail1 and other developmentally regulated transcription factors by YB-1 promotes an epithelial-mesenchymal transition. Cancer Cell, 2009, 15, 402-415.
Hsieh, A.C.; Liu, Y.; Edlind, M.P.; Ingolia, N.T.; Janes, M.R.; Sher, A.; Shi, E.Y.; Stumpf, C.R.; Christensen, C.; Bonham, M.J. The translational landscape of mTOR signalling steers cancer initiation and metastasis. Nature, 2012, 485, 55-61.
Heffler, E.; Allegra, A.; Pioggia, G.; Picardi, G.; Musolino, C.; Gangemi, S. MicroRNA profiling in asthma: potential biomarkers and therapeutic targets. Am. J. Respir. Cell Mol. Biol., 2017, 57(6), 642-650.
Allegra, A.; Musolino, C.; Tonacci, A.; Pioggia, G.; Gangemi, S. Interactions between the MicroRNAs and microbiota in cancer development: Roles and therapeutic opportunities. Cancers (Basel), 2020, 12(4), 805.
Allegra, A.; Alonci, A.; Campo, S.; Penna, G.; Petrungaro, A.; Gerace, D.; Musolino, C. Circulating microRNAs: new biomarkers in diagnosis, prognosis and treatment of cancer. Int. J. Oncol., 2012, 41(6), 1897-1912.
Blenkiron, C.; Hurley, D.G.; Fitzgerald, S.; Print, C.G.; Lasham, A. Links between the oncoprotein YB-1 and small non-coding RNAs in breast cancer. PLoS One, 2013, 8(11), e80171.
Das Gupta, A.; Krawczynska, N.; Nelson, E.R. Extracellular vesicles-the next frontier in endocrinology. Endocrinology, 2021, 162(9), bqab133.
Shurtleff, M.J.; Temoche-Diaz, M.M.; Karfilis, K.V.; Ri, S.; Schekman, R. Y-box protein 1 is required to sort microRNAs into exosomes in cells and in a cell-free reaction. eLife, 2016, 5, e19276.
Shurtleff, M.J.; Yao, J.; Qin, Y.; Nottingham, R.M.; Temoche-Diaz, M.M.; Schekman, R.; Lambowitz, A.M. Broad role for YBX1 in defining the small noncoding RNA composition of exosomes. Proc. Natl. Acad. Sci., 2017, 114(43), E8987-E8995.
Decker, C.J.; Parker, R. P-bodies and stress granules: possible roles in the control of translation and mRNA degradation. Cold Spring Harb. Perspect. Biol., 2012, 4(9), a012286.
Kedersha, N.; Anderson, P. Mammalian stress granules and processing bodies. Methods Enzymol., 2007, 431, 61-81.
Somasekharan, S.P.; El-Naggar, A.; Leprivier, G.; Cheng, H.; Hajee, S.; Grunewald, T.G.; Zhang, F.; Ng, T.; Delattre, O.; Evdokimova, V. YB-1 regulates stress granule formation and tumor progression by translationally activating G3BP1. J. Cell Biol., 2015, 208(7), 913-929.
Wang, L.; Wang, P.; Su, X.; Zhao, B. Circ_0001658 promotes the proliferation and metastasis of osteosarcoma cells via regulating miR-382-5p/YB-1 axis. Cell Biochem. Funct., 2020, 38(1), 77-86 .
[ 10.1002/cbf.3452]
Chen, J.; Han, S.; Chen, J.; Hu, P.; Zeng, Z.; Hu, Y.; Xiong, H.; Ke, Z.; Zhang, Y.; Xu, F.; Zhao, G. A reciprocal feedback of miR-548ac/YB-1/Snail induces EndMT of HUVECs during acidity microenvironment. Cancer Cell Int., 2021, 21(1), 692 .
Mehta, S.; Algie, M.; Al-Jabry, T.; McKinney, C.; Kannan, S.; Verma, C.S.; Ma, W.; Zhang, J.; Bartolec, T.K.; Masamsetti, V.P. Critical Role for Cold Shock Protein YB-1 in Cytokinesis. Cancers (Basel), 2020, 12(9), 2473.
Habibi, G.; Leung, S.; Law, J.H.; Gelmon, K.; Masoudi, H.; Turbin, D.; Pollak, M.; Nielsen, T.O.; Huntsman, D.; Dunn, S.E. Redefining prognostic factors for breast cancer: Yb-1 is a stronger predictor of relapse and disease-specific survival than estrogen receptor or her-2 across all tumor subtypes. Breast Cancer Res., 2008, 10, R86.
Lasham, A.; Samuel, W.; Cao, H.; Patel, R.; Mehta, R.; Stern, J.L.; Reid, G.; Woolley, A.G.; Miller, L.D.; Black, M.A. Yb-1, the e2f pathway, and regulation of tumor cell growth. J. Natl. Cancer Inst., 2011, 104, 133-146.
Woolley, A.G.; Algie, M.; Samuel, W.; Harfoot, R.; Wiles, A.; Hung, N.A.; Tan, P-H.; Hains, P.; Valova, V.A.; Huschtscha, L. Prognostic association of yb-1 expression in breast cancers: A matter of antibody. PLoS One, 2011, 6, e20603.
Ferreira, A.R.; Bettencourt, M.; Alho, I.; Costa, A.L.; Sousa, A.R.; Mansinho, A.; Abreu, C.; Pulido, C.; Macedo, D.; Vendrell, I.; Pacheco, T.R.; Costa, L.; Casimiro, S. Serum YB-1 (Y-box binding protein 1) as a biomarker of bone disease progression in patients with breast cancer and bone metastases. J. Bone Oncol., 2017, 6, 16-21.
Rohr, I.; Braicu, E.I.; En-Nia, A.; Heinrich, M.; Richter, R.; Chekerov, R.; Dechend, R.; Heidecke, H.; Dragun, D.; Schäfer, R.; Gorny, X.; Lindquist, J.A.; Brandt, S.; Sehouli, J.; Mertens, P.R. Y-box protein-1/p18 as novel serum marker for ovarian cancer diagnosis: A study by the tumor bank ovarian cancer (TOC). Cytokine, 2016, 85, 157-164.
Castellana, B.; Aasen, T.; Moreno-Bueno, G.; Dunn, S.E.; Ramón y Cajal, S. Interplay between YB-1 and IL-6 promotes the metastatic phenotype in breast cancer cells. Oncotarget, 2015, 6(35), 38239-38256 .
Wu, Q.; Parry, G. Hepsin and prostate cancer. Front. Biosci., 2007, 12, 5052-5059.
Zhang, C.; Zhang, M.; Wu, Q.; Peng, J.; Ruan, Y.; Gu, J. Hepsin inhibits CDK11p58 IRES activity by suppressing unr expression and eIF-2alpha phosphorylation in prostate cancer. Cell. Signal., 2015, 27(4), 789-797.
Martinez-Useros, J.; Georgiev-Hristov, T.; Fernandez-Acenero, M.J. UNR/CDSE1 expression as prognosis biomarker in resectable pancreatic ductal adenocarcinoma patients: a proof of-concept. PLoS One, 2017, 12(8), e0182044.
Tacke, F.; Galm, O.; Kanig, N.; Yagmur, E.; Brandt, S.; Lindquist, J.A.; Eberhardt, C.S.; Raffetseder, U.; Mertens, P.R. High prevalence of Y-box protein-1/p18 fragment in plasma of patients with malignancies of different origin. BMC Cancer, 2014, 14, 33.
Janz, M.; Harbeck, N.; Dettmar, P.; Berger, U.; Schmidt, A.; Jurchott, K.; Schmitt, M.; Royer, H.D. Y-box factor YB-1 predicts drug resistance and patient outcome in breast cancer independent of clinically relevant tumor biologic factors HER2, uPA and PAI-1. Int. J. Cancer, 2002, 97(3), 278-282.
Shibahara, K.; Sugio, K.; Osaki, T.; Uchiumi, T.; Maehara, Y.; Kohno, K.; Yasumoto, K.; Sugimachi, K.; Kuwano, M. Nuclear expression of the Ybox binding protein, YB-1, as a novel marker of disease progression in non-small cell lung cancer. Clin. Cancer Res., 2001, 7(10), 3151-3155.
Kamura, T.; Yahata, H.; Amada, S.; Ogawa, S.; Sonoda, T.; Kobayashi, H.; Mitsumoto, M.; Kohno, K.; Kuwano, M.; Nakano, H. Is nuclear expression of Y box-binding protein-1 a new prognostic factor in ovarian serous adenocarcinoma? Cancer, 1999, 85(11), 2450-2454.
Gimenez-Bonafe, P.; Fedoruk, M.N.; Whitmore, T.G.; Akbari, M.; Ralph, J.L.; Ettinger, S.; Gleave, M.E.; Nelson, C.C. YB-1 is upregulated during prostate cancer tumor progression and increases P-glycoprotein activity. Prostate, 2004, 59(3), 337-349.
Oda, Y.; Ohishi, Y.; Saito, T.; Hinoshita, E.; Uchiumi, T.; Kinukawa, N.; Iwamoto, Y.; Kohno, K.; Kuwano, M.; Tsuneyoshi, M. Nuclear expression of Y-box-binding protein-1 correlates with P-glycoprotein and topoisomerase II alpha expression, and with poor prognosis in synovial sarcoma. J. Pathol., 2003, 199(2), 251-258.
Oda, Y.; Kohashi, K.; Yamamoto, H.; Tamiya, S.; Kohno, K.; Kuwano, M.; Iwamoto, Y.; Tajiri, T.; Taguchi, T.; Tsuneyoshi, M. Different expression profiles of Y-box-binding protein-1 and multidrug resistance-associated proteins between alveolar and embryonal rhabdomyosarcoma. Cancer Sci., 2008, 99(4), 726-732.
Oda, Y.; Ohishi, Y.; Basaki, Y.; Kobayashi, H.; Hirakawa, T.; Wake, N.; Ono, M.; Nishio, K.; Kuwano, M.; Tsuneyoshi, M. Prognostic implications of the nuclear localization of Y-box-binding protein-1 and CXCR4 expression in ovarian cancer: their correlation with activated Akt, LRP/MVP and P-glycoprotein expression. Cancer Sci., 2007, 98(7), 1020-1026.
Oda, Y.; Sakamoto, A.; Shinohara, N.; Ohga, T.; Uchiumi, T.; Kohno, K.; Tsuneyoshi, M.; Kuwano, M.; Iwamoto, Y. Nuclear expression of YB-1 protein correlates with P-glycoprotein expression in human osteosarcoma. Clin. Cancer Res., 1998, 4(9), 2273-2277.
Saji, H.; Toi, M.; Saji, S.; Koike, M.; Kohno, K.; Kuwano, M. Nuclear expression of YB-1 protein correlates with P-glycoprotein expression in human breast carcinoma. Cancer Lett., 2003, 190(2), 191-197.
Dahl, E.; En-Nia, A.; Wiesmann, F.; Krings, R.; Djudjaj, S.; Breuer, E.; Fuchs, T.; Wild, P.J.; Hartmann, A.; Dunn, S.E.; Mertens, P.R. Nuclear detection of Y-box protein-1 (YB-1) closely associates with progesterone receptor negativity and is a strong adverse survival factor in human breast cancer. BMC Cancer, 2009, 9, 410 .
Chatterjee, M.; Rancso, C.; Stuhmer, T.; Eckstein, N.; Andrulis, M.; Gerecke, C.; Lorentz, H.; Royer, H.D.; Bargou, R.C. The Y-box binding protein YB-1 is associated with progressive disease and mediates survival and drug resistance in multiple myeloma. Blood, 2008, 111, 3714-3722.
Higashi, K.; Tomigahara, Y.; Shiraki, H.; Miyata, K.; Mikami, T. Kimura, T.; Moro, T.; Inagaki, Y.; Kaneko, H. A novel small compound that promotes nuclear translocation of YB-1 ameliorates experimental hepatic fibrosis in mice. J. Biol. Chem., 2011, 286(6), 4485-4492.
Higashi, K.; Inagaki, Y.; Fujimori, K.; Nakao, A.; Kaneko, H.; Nakatsuka, I. Interferon gamma interferes with transforming growth factor-beta signaling through direct interaction of YB-1 with Smad3. J. Biol. Chem., 2003, 278(44), 43470-43479.
Syed, D.N.; Adhami, V.M.; Khan, M.I.; Mukhtar, H. Inhibition of Akt/mTOR signaling by the dietary flavonoid fisetin. Anticancer. Agents Med. Chem., 2013, 13(7), 995-1001.
Gieseler-Halbach, S.; Meltendorf, S.; Pierau, M.; Weinert, S.; Heidel, F.H.; Fischer, T.; Handschuh, J.; Braun-Dullaeus, R.C.; Schrappe, M.; Lindquist, J.A. RSK-mediated nuclear accumulation of the cold-shock Y-box protein-1 controls proliferation of T cells and T-ALL blasts. Cell Death Differ., 2017, 24(2), 371-383.
Kato, M.; Wang, L.; Putta, S.; Wang, M.; Yuan, H.; Sun, G.; Lanting, L.; Todorov, I.; Rossi, J.J.; Natarajan, R. Post-transcriptional up-regulation of Tsc-22 by Ybx1, a target of miR-216a, mediates TGF-{beta}-induced collagen expression in kidney cells. J. Biol. Chem., 2010, 285(44), 34004-34015 .
Zhu, X.; Li, Y.; Shen, H.; Li, H.; Long, L.; Hui, L.; Xu, W. miR-137 restoration sensitizes multidrug-resistant MCF-7/ADM cells to anticancer agents by targeting YB-1. Acta Biochim. Biophys. Sin. (Shanghai), 2013, 45(2), 80-86.
Zeng, Y.; Kulkarni, P.; Inoue, T.; Getzenberg, R.H. Down-regulating cold shock protein genes impairs cancer cell survival and enhances chemosensitivity. J. Cell. Biochem., 2009, 107(1), 179-188.
Zhang, Y.; Wu, Y.; Mao, P.; Li, F.; Han, X.; Zhang, Y.; Jiang, S.; Chen, Y.; Huang, J.; Liu, D.; Zhao, Y.; Ma, W.; Songyang, Z. Cold-inducible RNA-binding protein CIRP/hnRNP A18 regulates telomerase activity in a temperature-dependent manner. Nucleic Acids Res., 2016, 44(2), 761-775 .
Meeker, A.K.; Coffey, D.S. Telomerase: a promising marker of biological immortality of germ, stem, and cancer cells. A review. Biochemistry (Mosc.), 1997, 62, 1323-1331.
Sakurai, T.; Yada, N.; Watanabe, T.; Arizumi, T.; Hagiwara, S.; Ueshima, K.; Nishida, N.; Fujita, J.; Kudo, M. Cold-inducible RNA-binding protein promotes the development of liver cancer. Cancer Sci., 2015, 106(4), 352-358.

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