Generic placeholder image

Current Medicinal Chemistry


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

Review Article

Research Progress of DCLK1 Inhibitors as Cancer Therapeutics

Author(s): Linna Cheng, Shenzhen Huang, Lijuan Chen, Xiaoyan Dong, Lei Zhang, Chengye Wu, Kaihong Ye, Fengmin Shao*, Zunmin Zhu* and Rick F. Thorne*

Volume 29, Issue 13, 2022

Published on: 09 July, 2021

Page: [2261 - 2273] Pages: 13

DOI: 10.2174/0929867328666210709110721

Price: $65


Doublecortin-like kinase 1 (DCLK1) has emerged over the last decade as a unique stem cell marker within gastrointestinal tissues. Evidence from mouse models shows that high Dclk1 expression denotes a population of cells that promote tissue regeneration and serve as potential cancer stem cells. Moreover, since certain DCLK1 isoforms are overexpressed in many cancers and not normal cells, targeting the expression or kinase activity of DCLK1 has the potential to inhibit cancer cell growth. Here, we review the evidence for DCLK1 as a prospective cancer target including its isoform-specific expression and mutational status in human cancers. We further discuss the challenges and current progress in the development of small molecule inhibitors of DCLK1.

Keywords: DCLK1, kinase inhibitor, cancer stem cell marker, structural biology, cancer biomarker, DCX.

Omori, Y.; Suzuki, M.; Ozaki, K.; Harada, Y.; Nakamura, Y.; Takahashi, E.; Fujiwara, T. Expression and chromosomal localization of KIAA0369, a putative kinase structurally related to Doublecortin. J. Hum. Genet., 1998, 43(3), 169-177.
[] [PMID: 9747029]
Sossey-Alaoui, K.; Srivastava, A.K. DCAMKL1, a brain-specific transmembrane protein on 13q12.3 that is similar to doublecortin (DCX). Genomics, 1999, 56(1), 121-126.
[] [PMID: 10036192]
Mizuguchi, M.; Qin, J.; Yamada, M.; Ikeda, K.; Takashima, S. High expression of doublecortin and KIAA0369 protein in fetal brain suggests their specific role in neuronal migration. Am. J. Pathol., 1999, 155(5), 1713-1721.
[] [PMID: 10550327]
Shu, T.; Tseng, H.C.; Sapir, T.; Stern, P.; Zhou, Y.; Sanada, K.; Fischer, A.; Coquelle, F.M.; Reiner, O.; Tsai, L.H. Doublecortin-like kinase controls neurogenesis by regulating mitotic spindles and M phase progression. Neuron, 2006, 49(1), 25-39.
[] [PMID: 16387637]
Lipka, J.; Kapitein, L.C.; Jaworski, J.; Hoogenraad, C.C. Microtubule-binding protein doublecortin-like kinase 1 (DCLK1) guides kinesin-3-mediated cargo transport to dendrites. EMBO J., 2016, 35(3), 302-318.
[] [PMID: 26758546]
Liu, J.S.; Schubert, C.R.; Fu, X.; Fourniol, F.J.; Jaiswal, J.K.; Houdusse, A.; Stultz, C.M.; Moores, C.A.; Walsh, C.A. Molecular basis for specific regulation of neuronal kinesin-3 motors by doublecortin family proteins. Mol. Cell, 2012, 47(5), 707-721.
[] [PMID: 22857951]
Kim, M.H.; Cierpicki, T.; Derewenda, U.; Krowarsch, D.; Feng, Y.; Devedjiev, Y.; Dauter, Z.; Walsh, C.A.; Otlewski, J.; Bushweller, J.H.; Derewenda, Z.S. The DCX-domain tandems of doublecortin and doublecortin-like kinase. Nat. Struct. Biol., 2003, 10(5), 324-333.
[] [PMID: 12692530]
Lin, P.T.; Gleeson, J.G.; Corbo, J.C.; Flanagan, L.; Walsh, C.A. DCAMKL1 encodes a protein kinase with homology to doublecortin that regulates microtubule polymerization. J. Neurosci., 2000, 20(24), 9152-9161.
[] [PMID: 11124993]
Nagase, T.; Ishikawa, K.; Suyama, M.; Kikuno, R.; Hirosawa, M.; Miyajima, N.; Tanaka, A.; Kotani, H.; Nomura, N.; Ohara, O. Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res., 1998, 5(6), 355-364.
[] [PMID: 10048485]
Tuy, F.P.; Saillour, Y.; Kappeler, C.; Chelly, J.; Francis, F. Alternative transcripts of Dclk1 and Dclk2 and their expression in doublecortin knockout mice. Dev. Neurosci., 2008, 30(1-3), 171-186.
[] [PMID: 18075264]
Deuel, T.A.; Liu, J.S.; Corbo, J.C.; Yoo, S.Y.; Rorke-Adams, L.B.; Walsh, C.A. Genetic interactions between doublecortin and doublecortin-like kinase in neuronal migration and axon outgrowth. Neuron, 2006, 49(1), 41-53.
[] [PMID: 16387638]
Koizumi, H.; Tanaka, T.; Gleeson, J.G. Doublecortin-like kinase functions with doublecortin to mediate fiber tract decussation and neuronal migration. Neuron, 2006, 49(1), 55-66.
[] [PMID: 16387639]
Le Hellard, S.; Håvik, B.; Espeseth, T.; Breilid, H.; Løvlie, R.; Luciano, M.; Gow, A.J.; Harris, S.E.; Starr, J.M.; Wibrand, K.; Lundervold, A.J.; Porteous, D.J.; Bramham, C.R.; Deary, I.J.; Reinvang, I.; Steen, V.M. Variants in doublecortin- and calmodulin kinase like 1, a gene up-regulated by BDNF, are associated with memory and general cognitive abilities. PLoS One, 2009, 4(10), e7534.
[] [PMID: 19844571]
Håvik, B.; Degenhardt, F.A.; Johansson, S.; Fernandes, C.P.; Hinney, A.; Scherag, A.; Lybæk, H.; Djurovic, S.; Christoforou, A.; Ersland, K.M.; Giddaluru, S.; O’Donovan, M.C.; Owen, M.J.; Craddock, N.; Mühleisen, T.W.; Mattheisen, M.; Schimmelmann, B.G.; Renner, T.; Warnke, A.; Herpertz-Dahlmann, B.; Sinzig, J.; Albayrak, Ö.; Rietschel, M.; Nöthen, M.M.; Bramham, C.R.; Werge, T.; Hebebrand, J.; Haavik, J.; Andreassen, O.A.; Cichon, S.; Steen, V.M.; Le Hellard, S. DCLK1 variants are associated across schizophrenia and attention deficit/hyperactivity disorder. PLoS One, 2012, 7(4), e35424.
[] [PMID: 22539971]
Monroy, B.Y.; Tan, T.C.; Oclaman, J.M.; Han, J.S.; Simó, S.; Niwa, S.; Nowakowski, D.W.; McKenney, R.J.; Ori-McKenney, K.M. A combinatorial map code dictates polarized microtubule transport. Dev. Cell, 2020, 53(1), 60-72.e4.
[] [PMID: 32109385]
Silverman, M.A.; Benard, O.; Jaaro, H.; Rattner, A.; Citri, Y.; Seger, R. CPG16, a novel protein serine/threonine kinase downstream of cAMP-dependent protein kinase. J. Biol. Chem., 1999, 274(5), 2631-2636.
[] [PMID: 9915791]
Shimomura, S.; Nagamine, T.; Hatano, N.; Sueyoshi, N.; Kameshita, I. Identification of an endogenous substrate of zebrafish doublecortin-like protein kinase using a highly active truncation mutant. J. Biochem., 2010, 147(5), 711-722.
[] [PMID: 20097902]
Nagamine, T.; Shimomura, S.; Sueyoshi, N.; Kameshita, I. Influence of Ser/Pro-rich domain and kinase domain of double cortin-like protein kinase on microtubule-binding activity. J. Biochem., 2011, 149(5), 619-627.
[] [PMID: 21278387]
Patel, O.; Dai, W.; Mentzel, M.; Griffin, M.D.; Serindoux, J.; Gay, Y.; Fischer, S.; Sterle, S.; Kropp, A.; Burns, C.J.; Ernst, M.; Buchert, M.; Lucet, I.S. Biochemical and structural insights into doublecortin-like kinase domain 1. Structure, 2016, 24(9), 1550-1561.
[] [PMID: 27545623]
Kruidering, M.; Schouten, T.; Evan, G.I.; Vreugdenhil, E. Caspase-mediated cleavage of the Ca2+/calmodulin-dependent protein kinase-like kinase facilitates neuronal apoptosis. J. Biol. Chem., 2001, 276(42), 38417-38425.
[] [PMID: 11479289]
Burgess, H.A.; Reiner, O. Cleavage of doublecortin-like kinase by calpain releases an active kinase fragment from a microtubule anchorage domain. J. Biol. Chem., 2001, 276(39), 36397-36403.
[] [PMID: 11473121]
Nagamine, T.; Nomada, S.; Onouchi, T.; Kameshita, I.; Sueyoshi, N. Nuclear translocation of doublecortin-like protein kinase and phosphorylation of a transcription factor JDP2. Biochem. Biophys. Res. Commun., 2014, 446(1), 73-78.
[] [PMID: 24582561]
May, R.; Riehl, T.E.; Hunt, C.; Sureban, S.M.; Anant, S.; Houchen, C.W. Identification of a novel putative gastrointestinal stem cell and adenoma stem cell marker, doublecortin and CaM kinase-like-1, following radiation injury and in adenomatous polyposis coli/multiple intestinal neoplasia mice. Stem Cells, 2008, 26(3), 630-637.
[] [PMID: 18055444]
Chandrakesan, P.; Weygant, N.; May, R.; Qu, D.; Chinthalapally, H.R.; Sureban, S.M.; Ali, N.; Lightfoot, S.A.; Umar, S.; Houchen, C.W. DCLK1 facilitates intestinal tumor growth via enhancing pluripotency and epithelial mesenchymal transition. Oncotarget, 2014, 5(19), 9269-9280.
[] [PMID: 25211188]
Li, J.; Wang, Y.; Ge, J.; Li, W.; Yin, L.; Zhao, Z.; Liu, S.; Qin, H.; Yang, J.; Wang, L.; Ni, B.; Liu, Y.; Wang, H. Doublecortin-like kinase 1 (dclk1) regulates b cell-specific moloney murine leukemia virus insertion site 1 (bmi-1) and is associated with metastasis and prognosis in pancreatic cancer. Cell. Physiol. Biochem., 2018, 51(1), 262-277.
[] [PMID: 30453285]
Wang, Y.L.; Li, Y.; Ma, Y.G.; Wu, W.Y. DCLK1 promotes malignant progression of breast cancer by regulating Wnt/β-Catenin signaling pathway. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(21), 9489-9498.
[PMID: 31773701]
Ali, N.; Allam, H.; May, R.; Sureban, S.M.; Bronze, M.S.; Bader, T.; Umar, S.; Anant, S.; Houchen, C.W. Hepatitis C virus-induced cancer stem cell-like signatures in cell culture and murine tumor xenografts. J. Virol., 2011, 85(23), 12292-12303.
[] [PMID: 21937640]
Weygant, N.; Qu, D.; May, R.; Tierney, R.M.; Berry, W.L.; Zhao, L.; Agarwal, S.; Chandrakesan, P.; Chinthalapally, H.R.; Murphy, N.T.; Li, J.D.; Sureban, S.M.; Schlosser, M.J.; Tomasek, J.J.; Houchen, C.W. DCLK1 is a broadly dysregulated target against epithelial-mesenchymal transition, focal adhesion, and stemness in clear cell renal carcinoma. Oncotarget, 2015, 6(4), 2193-2205.
[] [PMID: 25605241]
Whorton, J.; Sureban, S.M.; May, R.; Qu, D.; Lightfoot, S.A.; Madhoun, M.; Johnson, M.; Tierney, W.M.; Maple, J.T.; Vega, K.J.; Houchen, C.W. DCLK1 is detectable in plasma of patients with Barrett’s esophagus and esophageal adenocarcinoma. Dig. Dis. Sci., 2015, 60(2), 509-513.
[] [PMID: 25283374]
Gagliardi, G.; Goswami, M.; Passera, R.; Bellows, C.F. DCLK1 immunoreactivity in colorectal neoplasia. Clin. Exp. Gastroenterol., 2012, 5, 35-42.
[] [PMID: 22557932]
O’Connell, M.R.; Sarkar, S.; Luthra, G.K.; Okugawa, Y.; Toiyama, Y.; Gajjar, A.H.; Qiu, S.; Goel, A.; Singh, P. Epigenetic changes and alternate promoter usage by human colon cancers for expressing DCLK1-isoforms: Clinical Implications. Sci. Rep., 2015, 5, 14983.
[] [PMID: 26447334]
Baylin, S.B.; Jones, P.A. A decade of exploring the cancer epigenome - biological and translational implications. Nat. Rev. Cancer, 2011, 11(10), 726-734.
[] [PMID: 21941284]
Subramaniam, D.; Thombre, R.; Dhar, A.; Anant, S. DNA methyltransferases: a novel target for prevention and therapy. Front. Oncol., 2014, 4, 80.
[] [PMID: 24822169]
Vedeld, H.M.; Skotheim, R.I.; Lothe, R.A.; Lind, G.E. The recently suggested intestinal cancer stem cell marker DCLK1 is an epigenetic biomarker for colorectal cancer. Epigenetics, 2014, 9(3), 346-350.
[] [PMID: 24384857]
Vedeld, H.M.; Andresen, K.; Eilertsen, I.A.; Nesbakken, A.; Seruca, R.; Gladhaug, I.P.; Thiis-Evensen, E.; Rognum, T.O.; Boberg, K.M.; Lind, G.E. The novel colorectal cancer biomarkers CDO1, ZSCAN18 and ZNF331 are frequently methylated across gastrointestinal cancers. Int. J. Cancer, 2015, 136(4), 844-853.
[] [PMID: 24948044]
Sarkar, S.; O’Connell, M.R.; Okugawa, Y.; Lee, B.S.; Toiyama, Y.; Kusunoki, M.; Daboval, R.D.; Goel, A.; Singh, P. FOXD3 regulates csc marker, dclk1-s, and invasive potential: Prognostic implications in colon cancer. Mol. Cancer Res., 2017, 15(12), 1678-1691.
[] [PMID: 28851816]
Park, S.Y.; Kim, J.Y.; Choi, J.H.; Kim, J.H.; Lee, C.J.; Singh, P.; Sarkar, S.; Baek, J.H.; Nam, J.S. Inhibition of lef1-mediated dclk1 by niclosamide attenuates colorectal cancer stemness. Clin. Cancer Res., 2019, 25(4), 1415-1429.
[] [PMID: 30446587]
Shang, L.; Kwon, Y.G.; Nandy, S.; Lawrence, D.S.; Edelman, A.M. Catalytic and regulatory domains of doublecortin kinase-1. Biochem., 2003, 42(7), 2185-2194.
[] [PMID: 12590608]
Wang, K.; Yuen, S.T.; Xu, J.; Lee, S.P.; Yan, H.H.; Shi, S.T.; Siu, H.C.; Deng, S.; Chu, K.M.; Law, S.; Chan, K.H.; Chan, A.S.; Tsui, W.Y.; Ho, S.L.; Chan, A.K.; Man, J.L.; Foglizzo, V.; Ng, M.K.; Chan, A.S.; Ching, Y.P.; Cheng, G.H.; Xie, T.; Fernandez, J.; Li, V.S.; Clevers, H.; Rejto, P.A.; Mao, M.; Leung, S.Y. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat. Genet., 2014, 46(6), 573-582.
[] [PMID: 24816253]
Nagaraja, A.K.; Kikuchi, O.; Bass, A.J. Genomics and targeted therapies in gastroesophageal adenocarcinoma. Cancer Discov., 2019, 9(12), 1656-1672.
[] [PMID: 31727671]
Nakanishi, Y.; Seno, H.; Fukuoka, A.; Ueo, T.; Yamaga, Y.; Maruno, T.; Nakanishi, N.; Kanda, K.; Komekado, H.; Kawada, M.; Isomura, A.; Kawada, K.; Sakai, Y.; Yanagita, M.; Kageyama, R.; Kawaguchi, Y.; Taketo, M.M.; Yonehara, S.; Chiba, T. Dclk1 distinguishes between tumor and normal stem cells in the intestine. Nat. Genet., 2013, 45(1), 98-103.
[] [PMID: 23202126]
Bailey, J.M.; Alsina, J.; Rasheed, Z.A.; McAllister, F.M.; Fu, Y.Y.; Plentz, R.; Zhang, H.; Pasricha, P.J.; Bardeesy, N.; Matsui, W.; Maitra, A.; Leach, S.D. DCLK1 marks a morphologically distinct subpopulation of cells with stem cell properties in preinvasive pancreatic cancer. Gastroenterology, 2014, 146(1), 245-256.
[] [PMID: 24096005]
Lorenzo, N.; Sabina, D.M.; Guido, C.; Ilaria Grazia, Z.; Samira, S.; Valeria, A.; Daniele, C.; Diletta, O.; Antonella, G.; Marco, M.; Daniela, B.; Valerio, P.; Andrea, O.; Agostino Maria, R.; Fabio, M.; Maria Consiglia, B.; Jessica, F.; Sara, M.; Gian Luca, G.; Pierluigi Benedetti, P.; Paquale Bartomeo, B.; Felice, G.; Vincenzo, C.; Pietro, I.; Giuseppina, C.; Eugenio, G.; Domenico, A. DCLK1, a putative novel stem cell marker in human cholangiocarcinoma. Hepatology, 2021, 73(1), 144-159.
[] [PMID: 32978808]
Koren, E.; Fuchs, Y. The bad seed: Cancer stem cells in tumor development and resistance. Drug Resist. Updat., 2016, 28, 1-12.
[] [PMID: 27620951]
May, R.; Sureban, S.M.; Lightfoot, S.A.; Hoskins, A.B.; Brackett, D.J.; Postier, R.G.; Ramanujam, R.; Rao, C.V.; Wyche, J.H.; Anant, S.; Houchen, C.W. Identification of a novel putative pancreatic stem/progenitor cell marker DCAMKL-1 in normal mouse pancreas. Am. J. Physiol. Gastrointest. Liver Physiol., 2010, 299(2), G303-G310.
[] [PMID: 20522640]
Gerbe, F.; Brulin, B.; Makrini, L.; Legraverend, C.; Jay, P. DCAMKL-1 expression identifies Tuft cells rather than stem cells in the adult mouse intestinal epithelium. Gastroenterology, 2009, 137(6), 2179-2180.
[] [PMID: 19879217]
Saqui-Salces, M.; Keeley, T.M.; Grosse, A.S.; Qiao, X.T.; El-Zaatari, M.; Gumucio, D.L.; Samuelson, L.C.; Merchant, J.L. Gastric tuft cells express DCLK1 and are expanded in hyperplasia. Histochem. Cell Biol., 2011, 136(2), 191-204.
[] [PMID: 21688022]
Westphalen, C.B.; Asfaha, S.; Hayakawa, Y.; Takemoto, Y.; Lukin, D.J.; Nuber, A.H.; Brandtner, A.; Setlik, W.; Remotti, H.; Muley, A.; Chen, X.; May, R.; Houchen, C.W.; Fox, J.G.; Gershon, M.D.; Quante, M.; Wang, T.C. Long-lived intestinal tuft cells serve as colon cancer-initiating cells. J. Clin. Invest., 2014, 124(3), 1283-1295.
[] [PMID: 24487592]
Westphalen, C.B.; Takemoto, Y.; Tanaka, T.; Macchini, M.; Jiang, Z.; Renz, B.W.; Chen, X.; Ormanns, S.; Nagar, K.; Tailor, Y.; May, R.; Cho, Y.; Asfaha, S.; Worthley, D.L.; Hayakawa, Y.; Urbanska, A.M.; Quante, M.; Reichert, M.; Broyde, J.; Subramaniam, P.S.; Remotti, H.; Su, G.H.; Rustgi, A.K.; Friedman, R.A.; Honig, B.; Califano, A.; Houchen, C.W.; Olive, K.P.; Wang, T.C. Dclk1 defines quiescent pancreatic progenitors that promote injury-induced regeneration and tumorigenesis. Cell Stem Cell, 2016, 18(4), 441-455.
[] [PMID: 27058937]
Hayakawa, Y.; Sakitani, K.; Konishi, M.; Asfaha, S.; Niikura, R.; Tomita, H.; Renz, B.W.; Tailor, Y.; Macchini, M.; Middelhoff, M.; Jiang, Z.; Tanaka, T.; Dubeykovskaya, Z.A.; Kim, W.; Chen, X.; Urbanska, A.M.; Nagar, K.; Westphalen, C.B.; Quante, M.; Lin, C.S.; Gershon, M.D.; Hara, A.; Zhao, C.M.; Chen, D.; Worthley, D.L.; Koike, K.; Wang, T.C. Nerve growth factor promotes gastric tumorigenesis through aberrant cholinergic signaling. Cancer Cell, 2017, 31(1), 21-34.
[] [PMID: 27989802]
Kantara, C.; O’Connell, M.; Sarkar, S.; Moya, S.; Ullrich, R.; Singh, P. Curcumin promotes autophagic survival of a subset of colon cancer stem cells, which are ablated by DCLK1-siRNA. Cancer Res., 2014, 74(9), 2487-2498.
[] [PMID: 24626093]
Sakaguchi, M.; Hisamori, S.; Oshima, N.; Sato, F.; Shimono, Y.; Sakai, Y. miR-137 regulates the tumorigenicity of colon cancer stem cells through the inhibition of dclk1. Mol. Cancer Res., 2016, 14(4), 354-362.
[] [PMID: 26747706]
Panneerselvam, J.; Mohandoss, P.; Patel, R.; Gillan, H.; Li, M.; Kumar, K.; Nguyen, D.; Weygant, N.; Qu, D.; Pitts, K.; Lightfoot, S.; Rao, C.; Houchen, C.; Bronze, M.; Chandrakesan, P. DCLK1 regulates tumor stemness and cisplatin resistance in non-small cell lung cancer via abcd-member-4. Mol. Ther. Oncolytics, 2020, 18, 24-36.
[] [PMID: 32637578]
Qu, D.; Weygant, N.; Yao, J.; Chandrakesan, P.; Berry, W.L.; May, R.; Pitts, K.; Husain, S.; Lightfoot, S.; Li, M.; Wang, T.C.; An, G.; Clendenin, C.; Stanger, B.Z.; Houchen, C.W. Overexpression of DCLK1-AL Increases Tumor Cell Invasion, Drug Resistance, and KRAS Activation and Can Be Targeted to Inhibit Tumorigenesis in Pancreatic Cancer. J. Oncol., 2019, 2019, 6402925.
[] [PMID: 31467540]
Liao, T.T.; Yang, M.H. Revisiting epithelial-mesenchymal transition in cancer metastasis: the connection between epithelial plasticity and stemness. Mol. Oncol., 2017, 11(7), 792-804.
[] [PMID: 28649800]
Choi, E.; Petersen, C.P.; Lapierre, L.A.; Williams, J.A.; Weis, V.G.; Goldenring, J.R.; Nam, K.T. Dynamic expansion of gastric mucosal doublecortin-like kinase 1-expressing cells in response to parietal cell loss is regulated by gastrin. Am. J. Pathol., 2015, 185(8), 2219-2231.
[] [PMID: 26073039]
Mirzaei, A.; Tavoosidana, G.; Modarressi, M.H.; Rad, A.A.; Fazeli, M.S.; Shirkoohi, R.; Tavakoli-Yaraki, M.; Madjd, Z. Upregulation of circulating cancer stem cell marker, DCLK1 but not Lgr5, in chemoradiotherapy-treated colorectal cancer patients. Tumour Biol., 2015, 36(6), 4801-4810.
[] [PMID: 25631749]
Chandrakesan, P.; Yao, J.; Qu, D.; May, R.; Weygant, N.; Ge, Y.; Ali, N.; Sureban, S.M.; Gude, M.; Vega, K.; Bannerman-Menson, E.; Xia, L.; Bronze, M.; An, G.; Houchen, C.W. Dclk1, a tumor stem cell marker, regulates pro-survival signaling and self-renewal of intestinal tumor cells. Mol. Cancer, 2017, 16(1), 30.
[] [PMID: 28148261]
Makino, S.; Takahashi, H.; Okuzaki, D.; Miyoshi, N.; Haraguchi, N.; Hata, T.; Matsuda, C.; Yamamoto, H.; Mizushima, T.; Mori, M.; Doki, Y. DCLK1 integrates induction of TRIB3, EMT, drug resistance and poor prognosis in colorectal cancer. Carcinogenesis, 2020, 41(3), 303-312.
[] [PMID: 31562741]
Liu, W.; Wang, S.; Sun, Q.; Yang, Z.; Liu, M.; Tang, H. DCLK1 promotes epithelial-mesenchymal transition via the PI3K/Akt/NF-κB pathway in colorectal cancer. Int. J. Cancer, 2018, 142(10), 2068-2079.
[] [PMID: 29277893]
Howitt, M.R.; Lavoie, S.; Michaud, M.; Blum, A.M.; Tran, S.V.; Weinstock, J.V.; Gallini, C.A.; Redding, K.; Margolskee, R.F.; Osborne, L.C.; Artis, D.; Garrett, W.S. Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut. Science, 2016, 351(6279), 1329-1333.
[] [PMID: 26847546]
Wu, X.; Qu, D.; Weygant, N.; Peng, J.; Houchen, C.W. Cancer Stem Cell Marker DCLK1 Correlates with Tumorigenic Immune Infiltrates in the Colon and Gastric Adenocarcinoma Microenvironments. Cancers (Basel), 2020, 12(2), 274.
[] [PMID: 31979136]
Yan, R.; Li, J.; Zhou, Y.; Yao, L.; Sun, R.; Xu, Y.; Ge, Y.; An, G. Inhibition of DCLK1 down-regulates PD-L1 expression through Hippo pathway in human pancreatic cancer. Life Sci., 2020, 241, 117150.
[] [PMID: 31837335]
Zheng, Y.; Fang, Y.C.; Li, J. PD-L1 expression levels on tumor cells affect their immunosuppressive activity. Oncol. Lett., 2019, 18(5), 5399-5407.
[] [PMID: 31612048]
Wang, J.; Wang, S.; Zhou, J.; Qian, Q. miR-424-5p regulates cell proliferation, migration and invasion by targeting doublecortin-like kinase 1 in basal-like breast cancer. Biomed. Pharmacother., 2018, 102, 147-152.
[] [PMID: 29550638]
Sureban, S.M.; May, R.; Mondalek, F.G.; Qu, D.; Ponnurangam, S.; Pantazis, P.; Anant, S.; Ramanujam, R.P.; Houchen, C.W. Nanoparticle-based delivery of siDCAMKL-1 increases microRNA-144 and inhibits colorectal cancer tumor growth via a Notch-1 dependent mechanism. J. Nanobiotechnology, 2011, 9, 40.
[] [PMID: 21929751]
Sureban, S.M.; May, R.; Lightfoot, S.A.; Hoskins, A.B.; Lerner, M.; Brackett, D.J.; Postier, R.G.; Ramanujam, R.; Mohammed, A.; Rao, C.V.; Wyche, J.H.; Anant, S.; Houchen, C.W. DCAMKL-1 regulates epithelial-mesenchymal transition in human pancreatic cells through a miR-200a-dependent mechanism. Cancer Res., 2011, 71(6), 2328-2338.
[] [PMID: 21285251]
Sureban, S.; May, R.; Ramalingam, S.; Subramaniam, D.; Natarajan, G.; Anant, S.; Houchen, C. Selective blockade of DCAMKL-1 results in tumor growth arrest by a Let-7a MicroRNA-dependent mechanism. Gastroenterology, 2009, 137(2), 649-659. 659.e641-642.
Zhang, J.; Yang, P.L.; Gray, N.S. Targeting cancer with small molecule kinase inhibitors. Nat. Rev. Cancer, 2009, 9(1), 28-39.
[] [PMID: 19104514]
Mok, T.S.; Wu, Y.L.; Thongprasert, S.; Yang, C.H.; Chu, D.T.; Saijo, N.; Sunpaweravong, P.; Han, B.; Margono, B.; Ichinose, Y.; Nishiwaki, Y.; Ohe, Y.; Yang, J.J.; Chewaskulyong, B.; Jiang, H.; Duffield, E.L.; Watkins, C.L.; Armour, A.A.; Fukuoka, M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N. Engl. J. Med., 2009, 361(10), 947-957.
[] [PMID: 19692680]
Soria, J.C.; Ohe, Y.; Vansteenkiste, J.; Reungwetwattana, T.; Chewaskulyong, B.; Lee, K.H.; Dechaphunkul, A.; Imamura, F.; Nogami, N.; Kurata, T.; Okamoto, I.; Zhou, C.; Cho, B.C.; Cheng, Y.; Cho, E.K.; Voon, P.J.; Planchard, D.; Su, W.C.; Gray, J.E.; Lee, S.M.; Hodge, R.; Marotti, M.; Rukazenkov, Y.; Ramalingam, S.S. Osimertinib in untreated egfr-mutated advanced non-small-cell lung cancer. N. Engl. J. Med., 2018, 378(2), 113-125.
[] [PMID: 29151359]
Deng, X.; Dzamko, N.; Prescott, A.; Davies, P.; Liu, Q.; Yang, Q.; Lee, J.D.; Patricelli, M.P.; Nomanbhoy, T.K.; Alessi, D.R.; Gray, N.S. Characterization of a selective inhibitor of the Parkinson’s disease kinase LRRK2. Nat. Chem. Biol., 2011, 7(4), 203-205.
[] [PMID: 21378983]
Weygant, N.; Qu, D.; Berry, W.L.; May, R.; Chandrakesan, P.; Owen, D.B.; Sureban, S.M.; Ali, N.; Janknecht, R.; Houchen, C.W. Small molecule kinase inhibitor LRRK2-IN-1 demonstrates potent activity against colorectal and pancreatic cancer through inhibition of doublecortin-like kinase 1. Mol. Cancer, 2014, 13, 103.
[] [PMID: 24885928]
Yang, Q.; Deng, X.; Lu, B.; Cameron, M.; Fearns, C.; Patricelli, M.P.; Yates, J.R., III; Gray, N.S.; Lee, J.D. Pharmacological inhibition of BMK1 suppresses tumor growth through promyelocytic leukemia protein. Cancer Cell, 2010, 18(3), 258-267.
[] [PMID: 20832753]
Ferguson, F.M.; Nabet, B.; Raghavan, S.; Liu, Y.; Leggett, A.L.; Kuljanin, M.; Kalekar, R.L.; Yang, A.; He, S.; Wang, J.; Ng, R.W.S.; Sulahian, R.; Li, L.; Poulin, E.J.; Huang, L.; Koren, J.; Dieguez-Martinez, N.; Espinosa, S.; Zeng, Z.; Corona, C.R.; Vasta, J.D.; Ohi, R.; Sim, T.; Kim, N.D.; Harshbarger, W.; Lizcano, J.M.; Robers, M.B.; Muthaswamy, S.; Lin, C.Y.; Look, A.T.; Haigis, K.M.; Mancias, J.D.; Wolpin, B.M.; Aguirre, A.J.; Hahn, W.C.; Westover, K.D.; Gray, N.S. Discovery of a selective inhibitor of doublecortin like kinase 1. Nat. Chem. Biol., 2020, 16(6), 635-643.
[] [PMID: 32251410]
Cheetham, G.M. Novel protein kinases and molecular mechanisms of autoinhibition. Curr. Opin. Struct. Biol., 2004, 14(6), 700-705.
[] [PMID: 15582394]
Mayans, O.; van der Ven, P.F.; Wilm, M.; Mues, A.; Young, P.; Fürst, D.O.; Wilmanns, M.; Gautel, M. Structural basis for activation of the titin kinase domain during myofibrillogenesis. Nature, 1998, 395(6705), 863-869.
[] [PMID: 9804419]
Hu, S.H.; Parker, M.W.; Lei, J.Y.; Wilce, M.C.; Benian, G.M.; Kemp, B.E. Insights into autoregulation from the crystal structure of twitchin kinase. Nature, 1994, 369(6481), 581-584.
[] [PMID: 8202162]
Goldberg, J.; Nairn, A.C.; Kuriyan, J. Structural basis for the autoinhibition of calcium/calmodulin-dependent protein kinase I. Cell, 1996, 84(6), 875-887.
[] [PMID: 8601311]
Rosenberg, O.S.; Deindl, S.; Sung, R.J.; Nairn, A.C.; Kuriyan, J. Structure of the autoinhibited kinase domain of CaMKII and SAXS analysis of the holoenzyme. Cell, 2005, 123(5), 849-860.
[] [PMID: 16325579]
Mukherjee, K.; Sharma, M.; Urlaub, H.; Bourenkov, G.P.; Jahn, R.; Südhof, T.C.; Wahl, M.C. CASK functions as a mg2+-independent neurexin kinase. Cell, 2008, 133(2), 328-339.
[] [PMID: 18423203]
Ramakrishnan, C.; Mary Thangakani, A.; Velmurugan, D.; Anantha Krishnan, D.; Sekijima, M.; Akiyama, Y.; Gromiha, M.M. Identification of type I and type II inhibitors of c-Yes kinase using in silico and experimental techniques. J. Biomol. Struct. Dyn., 2018, 36(6), 1566-1576.
[] [PMID: 28589758]
Sureban, S.M.; May, R.; Weygant, N.; Qu, D.; Chandrakesan, P.; Bannerman-Menson, E.; Ali, N.; Pantazis, P.; Westphalen, C.B.; Wang, T.C.; Houchen, C.W. XMD8-92 inhibits pancreatic tumor xenograft growth via a DCLK1-dependent mechanism. Cancer Lett., 2014, 351(1), 151-161.
[] [PMID: 24880079]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy