De Novo Fatty Acid Synthesis-Driven Sphingolipid Metabolism Promotes Metastatic Potential of Colorectal Cancer

Molecular Cancer Research : MCR
Naser JafariYekaterina Y Zaytseva

Abstract

Metastasis is the most common cause of death in colorectal cancer patients. Fatty acid synthase (FASN) and sphingosine kinase-1 and -2 (SPHK1 and 2) are overexpressed in many cancers, including colorectal cancer. However, the contribution of FASN-mediated upregulation of sphingolipid metabolism to colorectal cancer metastasis and the potential of these pathways as targets for therapeutic intervention remain unknown. This study determined that sphingosine kinases (SPHK) are overexpressed in colorectal cancer as compared with normal mucosa. FASN expression significantly correlated with SPHK2 expression in data sets from The Cancer Genome Atlas (TCGA) and a colorectal cancer tumor microarray. FASN, SPHK1, and SPHK2 colocalized within invadopodia of primary colorectal cancer cells. Moreover, FASN inhibition decreased SPHK2 expression and the levels of dihydrosphingosine 1-phosphate (DH-S1P) and sphingosine 1-phosphate (S1P) in colorectal cancer cells and tumor tissues. Inhibition of FASN using TVB-3664 and sphingolipid metabolism using FTY-720 significantly inhibited the ability of primary colorectal cancer cells to proliferate, migrate, form focal adhesions, and degrade gelatin. Inhibition of the FASN/SPHK/S1P axis was accompanied...Continue Reading

References

Oct 19, 2001·Oncogene·S A Weed, J T Parsons
May 16, 2002·The Journal of Biological Chemistry·Sarah Spiegel, Sheldon Milstien
May 3, 2003·Nature Reviews. Molecular Cell Biology·Sarah Spiegel, Sheldon Milstien
Oct 9, 2003·The EMBO Journal·Stuart M PitsonBinks W Wattenberg
Mar 15, 2006·Cellular Signalling·Evgeny V BerdyshevViswanathan Natarajan
Jun 17, 2006·Current Opinion in Clinical Nutrition and Metabolic Care·Johannes V SwinnenGuido Verhoeven
Feb 22, 2007·The Journal of Biological Chemistry·Nitai C HaitSarah Spiegel
Jun 15, 2007·Critical Reviews in Oncology/hematology·Andrea Huwiler, Uwe Zangemeister-Wittke
Sep 21, 2007·Nature Reviews. Cancer·Javier A Menendez, Ruth Lupu
Jan 3, 2009·The Journal of Biological Chemistry·Evgeny V BerdyshevViswanathan Natarajan
Mar 9, 2010·Journal of Medicinal Chemistry·Thomas P MathewsTimothy L Macdonald
May 25, 2010·Cancer Science·Soichiro MurataNobuhiro Ohkohchi
Jun 18, 2010·Nature Reviews. Cancer·Nigel J Pyne, Susan Pyne
Jan 7, 2011·Cancer Biology & Therapy·Lindsay K RylandMark Kester
Mar 30, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jumpei KondoMasahiro Inoue
Jun 24, 2011·Nature Reviews. Molecular Cell Biology·Danielle A Murphy, Sara A Courtneidge
Sep 1, 2012·World Journal of Biological Chemistry·Feng Zhang, Guangwei Du
Dec 14, 2012·Nature Reviews. Cancer·Samy A F Morad, Myles C Cabot
Jan 16, 2013·Journal of Lipid Research·Hailan LiuJian-Ting Zhang
Sep 26, 2013·Biochimica Et Biophysica Acta·Mónica García-BarrosYusuf A Hannun
Dec 18, 2013·Carcinogenesis·Thomas N SeyfriedDominic P D'Agostino
Jun 28, 2014·Biomolecules·Anthony S DonTimothy A Couttas
Jul 30, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Li ZhangJianguo Xu
Dec 15, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jianting LongShi Fang
Jan 7, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Lan ZhangYanmei Ma
Apr 2, 2016·Oncotarget·Christopher WhiteDmitri Pchejetski
Dec 3, 2016·Nature Reviews. Cancer·Colin D PaulKonstantinos Konstantopoulos
Feb 17, 2017·Pharmacology & Therapeutics·Douglas BuckleyGeorge Kemble
Jul 8, 2017·Molecular Biology of the Cell·Chiara De Pascalis, Sandrine Etienne-Manneville

❮ Previous
Next ❯

Citations

Jul 14, 2019·The Journal of Pharmacology and Experimental Therapeutics·Leslie E LupienPaul W Baures
May 28, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Petra Grbčić, Mirela Sedić
Mar 21, 2020·Archives of Oral Biology·Iara Gonçalves de AquinoEdgard Graner
Jan 20, 2021·Nature Reviews. Cancer·Gabriele Bergers, Sarah-Maria Fendt
Dec 23, 2020·International Journal of Molecular Sciences·Nagendra S YarlaChinthalapally V Rao
Nov 22, 2020·Molecular Aspects of Medicine·Elena PiccininAntonio Moschetta
Oct 8, 2020·Pathology, Research and Practice·Yijiao YuanZuohui Zhao
Jul 11, 2021·Cellular Signalling·Real Sumayya Abdul SattarSundeep Singh Saluja
Jul 8, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yufeng HuHongliang Li

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.