Could Drugs Inhibiting the Mevalonate Pathway Also Target Cancer Stem Cells?

Could Drugs Inhibiting the Mevalonate Pathway Also Target Cancer Stem Cells? Publisher Pubmed

Likus W¹ ; Siemianowicz K² ; Bienk K³ ; Pakula M⁴ ; Pathak H⁵ ; Dutta C⁶ ; Wang Q⁷ ; Shojaei S⁸ ; Assaraf YG⁹ ; Ghavami S^{10, 11} ; Cieslarpobuda A¹² ; Los MJ^{13, 14}

Show Affiliations

1. Department of Human Anatomy, School of Medicine in Katowice, Medical University of Silesia, 18 Medykow Street, Katowice, 40-752, Poland
2. Department of Biochemistry, School of Medicine in Katowice, Medical University of Silesia, 18 Medykow Street, Katowice, 40-752, Poland
3. Interdisciplinary Nanoscience Center (INANO), Aarhus University, Aarhus C, DK-8000, Denmark
4. Department of Biomedicine, Aarhus University, Aarhus C, DK-8000, Denmark
5. Indian Institute of Science Education and Research (IISER TVM), Thiruvananthapuram, Kerala, India
6. Department of Clinical and Experimental Medicine (IKE), Linkoping University, Linkoping, Sweden
7. Department of Physics, Chemistry and Biology (IFM), Division of Biotechnology, Linkoping University, Linkoping, Sweden
8. Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
9. Fred Wyszkowski Cancer Research Laboratory, Department of Biology, Technion-Israel Institute of Technology, Haifa, 32000, Israel
10. Department of Human Anatomy and Cell Science, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
11. Health Research Policy Center, Shiraz University of Medical Science, Shiraz, Iran
12. Institute of Automatic Control, Silesian University of Technology, Gliwice, Poland
13. LinkoCare Life Sciences AB, Linkoping, 583 30, Sweden
14. ENT Department, School of Medicine in Katowice, Medical University of Silesia, 20-24 Francuska Street, Katowice, 40-027, Poland

Source: Drug Resistance Updates Published:2016

Abstract

Understanding the connection between metabolic pathways and cancer is very important for the development of new therapeutic approaches based on regulatory enzymes in pathways associated with tumorigenesis. The mevalonate cascade and its rate-liming enzyme HMG CoA-reductase has recently drawn the attention of cancer researchers because strong evidences arising mostly from epidemiologic studies, show that it could promote transformation. Hence, these studies pinpoint HMG CoA-reductase as a candidate proto-oncogene. Several recent epidemiological studies, in different populations, have proven that statins are beneficial for the treatment-outcome of various cancers, and may improve common cancer therapy strategies involving alkylating agents, and antimetabolites. Cancer stem cells/cancer initiating cells (CSC) are key to cancer progression and metastasis. Therefore, in the current review we address the different effects of statins on cancer stem cells. The mevalonate cascade is among the most pleiotropic, and highly interconnected signaling pathways. Through G-protein-coupled receptors (GRCP), it integrates extra-, and intracellular signals. The mevalonate pathway is implicated in cell stemness, cell proliferation, and organ size regulation through the Hippo pathway (e.g. Yap/Taz signaling axis). This pathway is a prime preventive target through the administration of statins for the prophylaxis of obesity-related cardiovascular diseases. Its prominent role in regulation of cell growth and stemness also invokes its role in cancer development and progression. The mevalonate pathway affects cancer metastasis in several ways by: (i) affecting epithelial-to-mesenchymal transition (EMT), (ii) affecting remodeling of the cytoskeleton as well as cell motility, (iii) affecting cell polarity (non-canonical Wnt/planar pathway), and (iv) modulation of mesenchymal-to-epithelial transition (MET). Herein we provide an overview of the mevalonate signaling network. We then briefly highlight diverse functions of various elements of this mevalonate pathway. We further discuss in detail the role of elements of the mevalonate cascade in stemness, carcinogenesis, cancer progression, metastasis and maintenance of cancer stem cells. © 2016 The Authors.

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Style	Citing Format
MLA	Likus W, et al.. "Could Drugs Inhibiting the Mevalonate Pathway Also Target Cancer Stem Cells?." Drug Resistance Updates, vol. 25, no. , 2016, pp. 13-25.
APA	Likus W, Siemianowicz K, Bienk K, Pakula M, Pathak H, Dutta C, Wang Q, Shojaei S, Assaraf YG, Ghavami S, Cieslarpobuda A, Los MJ (2016). Could Drugs Inhibiting the Mevalonate Pathway Also Target Cancer Stem Cells?. Drug Resistance Updates, 25(), 13-25.
Chicago	Likus W, Siemianowicz K, Bienk K, Pakula M, Pathak H, Dutta C, Wang Q, et al.. "Could Drugs Inhibiting the Mevalonate Pathway Also Target Cancer Stem Cells?." Drug Resistance Updates 25, no. (2016): 13-25.
Harvard	Likus W et al. (2016) 'Could Drugs Inhibiting the Mevalonate Pathway Also Target Cancer Stem Cells?', Drug Resistance Updates, 25(), pp. 13-25.
Vancouver	Likus W, Siemianowicz K, Bienk K, Pakula M, Pathak H, Dutta C, et al.. Could Drugs Inhibiting the Mevalonate Pathway Also Target Cancer Stem Cells?. Drug Resistance Updates. 2016;25():13-25.
BibTex	@article{ author = {Likus W and Siemianowicz K and Bienk K and Pakula M and Pathak H and Dutta C and Wang Q and Shojaei S and Assaraf YG and Ghavami S and Cieslarpobuda A and Los MJ}, title = {Could Drugs Inhibiting the Mevalonate Pathway Also Target Cancer Stem Cells?}, journal = {Drug Resistance Updates}, volume = {25}, number = {}, pages = {13-25}, year = {2016} }
RIS	TY - JOUR AU - Likus W AU - Siemianowicz K AU - Bienk K AU - Pakula M AU - Pathak H AU - Dutta C AU - Wang Q AU - Shojaei S AU - Assaraf YG AU - Ghavami S AU - Cieslarpobuda A AU - Los MJ TI - Could Drugs Inhibiting the Mevalonate Pathway Also Target Cancer Stem Cells? JO - Drug Resistance Updates VL - 25 IS - SP - 13 EP - 25 PY - 2016 ER -

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