Deleted in liver cancer 2 suppresses cell growth via the regulation of the Raf-1-ERK1/2-p70S6K signalling pathway

Liver International : Official Journal of the International Association for the Study of the Liver
Thomas Ho-Yin LeungIrene Oi-lin Ng

Abstract

Deleted in liver cancer 2 (DLC2) gene, a putative tumour suppressor gene, encodes a Rho GTPase-activating protein (RhoGAP) with GAP activity specific for RhoA. It exhibits tumour suppressor functions and inhibits tumour cell proliferation, migration as well as transformation. In this study, we aimed to investigate the underlying mechanisms of the DLC2 gene in suppressing cell migration and cell growth. HepG2 hepatoma cells were stably transfected with the DLC2γ isoform, which contains the RhoGAP domain. On performing immunofluorescence staining and Western blot analysis, the expression of the focal adhesion protein paxillin was found to be much reduced in DLC2γ-stable clones. Upon flow cytometric analysis of the cell cycle profiles, the DLC2γ-stable clones were shown to have a higher population of cells arrested at the G1 phase than the EGFP vector-stable clone, suggesting that downregulation of RhoA activity in DLC2γ-stable clones inhibited cell cycle progression. In the DLC2γ-stable clone, the levels of Raf-1 and extracellular signal-regulated kinase (ERK) 1/2 were decreased as compared with those of the parental HepG2, EGFP vector and DLC2γ-GAP defective mutant-stable clones. Furthermore, the ribosomal kinase p70S6K, a downs...Continue Reading

References

Apr 1, 1997·Current Opinion in Cell Biology·D K Morrison, R E Cutler
Jul 8, 1999·Nature Medicine·J S Sebolt-LeopoldA R Saltiel
Nov 1, 2000·Cell·D Bar-Sagi, A Hall
Jul 18, 2001·The Journal of Biological Chemistry·W LiK L Guan
Nov 21, 2001·Nature Cell Biology·C F WelshR K Assoian
Apr 21, 2004·The Journal of Biological Chemistry·Akiko MammotoDonald E Ingber
Dec 30, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Fikret SahinMichael Torbenson
Aug 30, 2005·Journal of the American College of Surgeons·Shinji OsadaYasuyuki Sugiyama
Oct 12, 2005·Proceedings of the National Academy of Sciences of the United States of America·Thomas Ho-Yin LeungIrene Oi-Lin Ng
Oct 23, 2009·Liver International : Official Journal of the International Association for the Study of the Liver·Ivan Chun-Fai HuiIrene Oi-Lin Ng

❮ Previous
Next ❯

Citations

Jan 16, 2013·Journal of Receptor and Signal Transduction Research·Sally El-Sitt, Mirvat El-Sibai
Mar 24, 2012·PloS One·Zhu-mei ShiBing-Hua Jiang
Apr 11, 2020·Human Cell·Leila JaafarMirvat El-Sibai
Sep 22, 2019·Journal of Cellular and Molecular Medicine·Zhixin QiuWeimin Li
Aug 3, 2021·Computational and Mathematical Methods in Medicine·Xuhui WuJichun Liu

❮ Previous
Next ❯

Related Concepts

Related Feeds

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.