Experimental evidence of Migfilin as a new therapeutic target of hepatocellular carcinoma metastasis

Experimental Cell Research
Vasiliki Gkretsi, Dimitrios P Bogdanos

Abstract

Migfilin is a novel cell-matrix adhesion protein known to interact with Vasodilator Stimulated Phosphoprotein (VASP) and be localized both at cell-matrix and cell-cell adhesions. To date there is nothing known about its role in hepatocellular carcinoma (HCC). As matrix is important in metastasis, we aimed to investigate the Migfilin׳s role in HCC metastasis using two human HCC cell lines that differ in their metastatic potential; non-invasive Alexander cells and the highly invasive HepG2 cells. We silenced Migfilin by siRNA and studied its effect on signaling and metastasis-related cellular properties. We show that Migfilin׳s expression is elevated in HepG2 cells and its silencing leads to upregulation of actin reorganization-related proteins, namely phosphor-VASP (Ser157 and Ser239), Fascin-1 and Rho-kinase-1, promoting actin polymerization and inhibiting cell invasion. Phosphor-Akt (Ser473) is decreased contributing to the upregulation of free and phosphor-β-catenin (Ser33/37Thr41) and inducing proliferation. Migfilin elimination upregulates Extracellular Signal-regulated kinase, which increases cell adhesion in HepG2 and reduces invasiveness. This is the first study to reveal that Migfilin inhibition can halt HCC metastasis ...Continue Reading

References

May 2, 2003·Nature Reviews. Cancer·Thomas W KenslerJohn D Groopman
Jun 5, 2003·Nature Reviews. Molecular Cell Biology·Kirsi Riento, Anne J Ridley
Jul 3, 2003·Trends in Cell Biology·Adam V KwiatkowskiJoseph J Loureiro
Feb 24, 2004·Frontiers in Bioscience : a Journal and Virtual Library·Antonio S Sechi, Juergen Wehland
Jan 27, 2005·Journal of Cell Science·Vasiliki GkretsiChuanyue Wu
Aug 22, 2009·Journal of Surgical Oncology·Tomohiro IguchiMasazumi Tsuneyoshi
Oct 15, 2009·Journal of Cell Science·Peter M BenzThomas Renné
Oct 17, 2009·The Journal of Biological Chemistry·Jianping ZhaoChuanyue Wu
Oct 26, 2011·Nature Reviews. Gastroenterology & Hepatology·Yan LiJin-Xuan Hou
Apr 13, 2012·European Journal of Gastroenterology & Hepatology·Xiaodan HuangGuozhong Ji
May 5, 2012·The Journal of Biological Chemistry·Guozhi XiaoChuanyue Wu
Mar 5, 2014·Proceedings of the National Academy of Sciences of the United States of America·Jonathan D WinkelmanDavid R Kovar

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Citations

Oct 24, 2017·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Kikuko HottaAtsushi Nakajima
Jul 29, 2018·Journal of Experimental & Clinical Cancer Research : CR·Ning BaiZhiming Wang
Dec 7, 2018·Frontiers in Genetics·Yaroslav R EfremovSergey S Bogachev
Jan 10, 2019·International Journal of Molecular Sciences·Vasiliki GkretsiTriantafyllos Stylianopoulos

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