Abstract
Sphingosine kinases (Sphk1 and 2) regulate the prodution of sphingosine-1-phosphate (S1P), that is key molecule in cancer development. SphK1, which is commonly overexpressed in malignant tumours, significantly contributes to the pathogenesis of various types of cancer as well as to resistance to different Tyrosine Kinase inibitors (TKIs). Even, SphK2 may promote apoptosis and inhibit cell growth but its role has not yet been fully understood in pathologic conditions. Different growth factorsinduced activation of receptor tyrosine kinases (RTKs) results in production of Sphk1 which catalyzes the phosphorylation of sphingosine. Such enzyme, in turn, is involved in many cellular processes by its five receptors. These are able to transactivate RTKs through amplification of a positive-feedback signaling loop. In conclusion, development of pharmacological inhibitors of SphK1 has been limited by the lack of completely understanding of the enzymatic activation mechanisms of SphK1.
Keywords: Cancer, receptor tyrosine kinases (RTKs), sphingosine kinase 1 (SphK1), sphingolipids, sphingosine 1-phosphate (S1P), tyrosine kinase inibitors (TKIs).
Mini-Reviews in Medicinal Chemistry
Title:Sphingosine Kinases Signalling in Carcinogenesis
Volume: 15 Issue: 4
Author(s): Gabriella Marfe, Giovanna Mirone, Arvind Shukla and Carla Di Stefano
Affiliation:
Keywords: Cancer, receptor tyrosine kinases (RTKs), sphingosine kinase 1 (SphK1), sphingolipids, sphingosine 1-phosphate (S1P), tyrosine kinase inibitors (TKIs).
Abstract: Sphingosine kinases (Sphk1 and 2) regulate the prodution of sphingosine-1-phosphate (S1P), that is key molecule in cancer development. SphK1, which is commonly overexpressed in malignant tumours, significantly contributes to the pathogenesis of various types of cancer as well as to resistance to different Tyrosine Kinase inibitors (TKIs). Even, SphK2 may promote apoptosis and inhibit cell growth but its role has not yet been fully understood in pathologic conditions. Different growth factorsinduced activation of receptor tyrosine kinases (RTKs) results in production of Sphk1 which catalyzes the phosphorylation of sphingosine. Such enzyme, in turn, is involved in many cellular processes by its five receptors. These are able to transactivate RTKs through amplification of a positive-feedback signaling loop. In conclusion, development of pharmacological inhibitors of SphK1 has been limited by the lack of completely understanding of the enzymatic activation mechanisms of SphK1.
Export Options
About this article
Cite this article as:
Marfe Gabriella, Mirone Giovanna, Shukla Arvind and Di Stefano Carla, Sphingosine Kinases Signalling in Carcinogenesis, Mini-Reviews in Medicinal Chemistry 2015; 15 (4) . https://dx.doi.org/10.2174/1389557515666150227105415
DOI https://dx.doi.org/10.2174/1389557515666150227105415 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from the ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Peroxisome Proliferator Activated Receptor α Ligands as Anticancer Drugs Targeting Mitochondrial Metabolism
Current Pharmaceutical Biotechnology Non-Steroidal Targets in the Diagnosis and Treatment of Endometriosis
Current Medicinal Chemistry Treatment of Leishmaniasis: A Review and Assessment of Recent Research
Current Pharmaceutical Design Achievements and Challenges of Proteomics in the Study of Rheumatoid Arthritis
Current Topics in Medicinal Chemistry Oncogene Expression Modulation in Cancer Cell Lines by DNA G-Quadruplex-Interactive Small Molecules
Current Medicinal Chemistry Molecular Targets and Targeted Therapies for Malignant Mesothelioma
Current Medicinal Chemistry Skeletal Effects of Drugs to Treat Cancer
Current Drug Safety Highlights on Important Medicinal Plants for the Menopause Syndrome
Current Women`s Health Reviews Antimicrobial, Antineoplastic and Cytotoxic Activities of Indole Alkaloids from Tabernaemontana divaricata (L.) R.Br.
Current Pharmaceutical Analysis Angiogenesis and Anti-angiogenic Therapies in Epithelial Ovarian Cancer
Current Angiogenesis (Discontinued) Synthetic 2-Methoxyestradiol Derivatives: Structure-Activity Relationships
Current Medicinal Chemistry Novel Function of Beta 2 Glycoprotein I in Angiogenesis
Current Angiogenesis (Discontinued) Counselling and Cognitive Behaviour Interventions Delivered to Reduce Psychological Morbidity and Improve Quality of Life in Gynaecological Cancer Patients: Recent Achievements
Current Women`s Health Reviews Crosstalk of Long Non-coding RNAs and EMT: Searching the Missing Pieces of an Incomplete Puzzle for Lung Cancer Therapy
Current Cancer Drug Targets Nonviral Approach for Targeted Nucleic Acid Delivery
Current Medicinal Chemistry Future Targets in Endometriosis Treatment: Targeting the Endometriotic Implant
Mini-Reviews in Medicinal Chemistry Plant Troponoids: Chemistry, Biological Activity, and Biosynthesis
Current Medicinal Chemistry Thrombophilia and Female Sex Hormones
Current Women`s Health Reviews Cancer Chemoprevention by Targeting the Epigenome
Current Drug Targets Basic Mechanisms Involved in the Anti-Cancer Effects of Melatonin
Current Medicinal Chemistry