Knockdown of CD44 inhibits the invasion and metastasis of hepatocellular carcinoma both in vitro and in vivo by reversing epithelial-mesenchymal transition

Oncotarget
Yuan GaoKefeng Dou

Abstract

Mounting evidence has shown that induction of epithelial-mesenchymal transition (EMT) contributes to the the expression of CSC (cancer stem cell) markers. However, whether and how CSC markers could be involved in regulating EMT has rarely been reported. CD44, being one of the most commonly used CSC markers in hepatocellular carcinoma (HCC), has been demonstrated to act as a multidomain, transmembrane platform that serves to integrate a wide variety of extracellular signals. Therefore, we determined to seek whether CD44 is necessary for the EMT process in HCC. First, we noticed that CD44 expression was associated with the mesenchymal phenotype in HCC cell lines, and knocking down CD44 with lentivirus-mediated shRNA in HCC cell lines resulted in the mesenchymal-epithelial-transition (MET) and the subsequent impaired migration and invasion in vitro. Moreover, in a metastatic mice model established by tail vein injection of luciferase labelled MHCC97-H cells, we confirmed that CD44 knockdown resulted in the decreased metastasis of HCC cells. Furthermore, we found that the induction of MET by CD44 inhibition might be achieved, at least in part, by repressing the ERK/Snail pathway.

References

Jun 16, 2001·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·R T PoonJ Wong
Dec 5, 2002·Genes & Development·Véronique Orian-RousseauHelmut Ponta
Aug 3, 2004·Oncogene·Maria José BarberàAntonio García de Herreros
Jun 13, 2006·IUBMB Life·Karoline J Briegel
Sep 28, 2006·Annual Review of Medicine·Piero DalerbaMichael F Clarke
Oct 27, 2006·Molecular Biology of the Cell·Véronique Orian-RousseauHelmut Ponta
Nov 28, 2006·Biochimica Et Biophysica Acta·James A McCubreyRichard A Franklin
Aug 7, 2008·PloS One·Anne-Pierre MorelAlain Puisieux
Jan 27, 2009·Cancer Metastasis Reviews·Mahmut Yilmaz, Gerhard Christofori
Mar 6, 2009·Nature Reviews. Cancer·Kornelia Polyak, Robert A Weinberg
Jun 10, 2009·The Journal of Cell Biology·Jia-Lin LeeJeou-Yuan Chen
Oct 13, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Muh-Hwa YangJaw-Ching Wu
Aug 10, 2010·BMC Cancer·Poornima Bhat-NakshatriHarikrishna Nakshatri
Mar 26, 2011·Science·Christine L Chaffer, Robert A Weinberg
Jun 28, 2011·The EMBO Journal·Ying-Jhen SuJia-Lin Lee
Jan 24, 2012·Cell·Andrew D RhimBen Z Stanger
Feb 23, 2012·Lancet·Alejandro FornerJordi Bruix
Jun 19, 2012·International Journal of Clinical Oncology·Lkhagva-Ochir TovuuMitsuo Shimada
Nov 21, 2012·Journal of Cell Science·Ruby Yun-Ju HuangJean Paul Thiery
Dec 1, 2012·Current Opinion in Oncology·Yoko KatsunoRik Derynck
Jun 27, 2013·Oncotarget·Youhei KimuraAkio Yamaguchi
Aug 3, 2013·WormBook : the Online Review of C. Elegans Biology·Meera V Sundaram
Feb 22, 2014·Nature Reviews. Molecular Cell Biology·Samy LamouilleRik Derynck
May 31, 2014·Nature Cell Biology·Alain PuisieuxJulie Caramel
Aug 2, 2014·Advances in Cancer Research·Véronique Orian-Rousseau, Jonathan Sleeman

❮ Previous
Next ❯

Citations

Oct 1, 2019·Anti-cancer Agents in Medicinal Chemistry·Jaleh VarshosazFarshid Hassanzadeh
Mar 27, 2020·Frontiers in Pharmacology·Yafei WuQin Li
Oct 10, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Zeyu LinNengtai Ouyang
Jan 23, 2020·World Journal of Gastrointestinal Oncology·Miao FangDeng-Fu Yao
Sep 13, 2019·Cell Death and Differentiation·Ruo-Yu ChenLiang-Yi Hung
Sep 28, 2017·International Journal of Molecular Medicine·Chien-Hung LinYann-Jang Chen
Jan 30, 2020·Vaccines·Gabriel SiracusanoLucia Lopalco
Jun 27, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Keiko TakagiNoboru Fukuda
Nov 29, 2016·Oncogene·M KumazoeH Tachibana
Mar 25, 2016·Oncotarget·Charmina Aguirre-AlvaradoMarco A Velasco-Velázquez
Sep 1, 2016·Journal of Hematology & Oncology·Aparna JayachandranJason C Steel
Jun 28, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Xiao-Qiang GaoHua-Xing Ma
Jan 10, 2019·Therapeutic Advances in Medical Oncology·Nuozhou WangGeorge G Chen
Apr 7, 2021·Experimental Biology and Medicine·Wen YinY James Kang
Apr 25, 2021·Molecular Biology Reports·Magdelyn Mei-Theng WongSin-Yeang Teow
Aug 28, 2021·Cancers·Yen-Yun WangShyng-Shiou F Yuan

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection

Software Mentioned

iQ5 Optical System
SPSS
Image Lab

Related Concepts

Related Feeds

Carcinoma, Hepatocellular

Hepatocellular Carcinoma is a malignant cancer in liver epithelial cells. Discover the latest research on Hepatocellular Carcinoma 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.

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.