CD44s regulates the TGF-β-mediated mesenchymal phenotype and is associated with poor prognosis in patients with hepatocellular carcinoma

Cancer Research
Kosuke MimaHideo Baba

Abstract

The prognosis for individuals diagnosed with hepatocellular carcinoma (HCC) remains poor because of the high frequency of invasive tumor growth, intrahepatic spread, and extrahepatic metastasis. Here, we investigated the role of the standard isoform of CD44 (CD44s), a major adhesion molecule of the extracellular matrix and a cancer stem cell marker, in the TGF-β-mediated mesenchymal phenotype of HCC. We found that CD44s was the dominant form of CD44 mRNA expressed in HCC cells. Overexpression of CD44s promoted tumor invasiveness and increased the expression of vimentin, a mesenchymal marker, in HCC cells. Loss of CD44s abrogated these changes. Also in the setting of CD44s overexpression, treatment with TGF-β1 induced the mesenchymal phenotype of HCC cells, which was characterized by low E-cadherin and high vimentin expression. Loss of CD44s inhibited TGF-β-mediated vimentin expression, mesenchymal spindle-like morphology, and tumor invasiveness. Clinically, overexpression of CD44s was associated with low expression of E-cadherin, high expression of vimentin, a high percentage of phospho-Smad2-positive nuclei, and poor prognosis in HCC patients, including reduced disease-free and overall survival. Together, our findings suggest ...Continue Reading

References

Feb 1, 1992·In Vitro Cellular & Developmental Biology : Journal of the Tissue Culture Association·S C HeffelfingerG J Darlington
Apr 7, 1997·Biochemical and Biophysical Research Communications·S Hiscox, W G Jiang
Apr 29, 1999·American Journal of Surgery·M Abou-ShadyM W Büchler
Jun 16, 2001·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·R T PoonJ Wong
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jan 4, 2003·Nature Reviews. Molecular Cell Biology·Helmut PontaPeter A Herrlich
Mar 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·Muhammad Al-HajjMichael F Clarke
Sep 27, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Terence K LeeSheung Tat Fan
Jan 11, 2007·Proceedings of the National Academy of Sciences of the United States of America·M E PrinceL E Ailles
Feb 7, 2007·Cancer Research·Chenwei LiDiane M Simeone
Jun 6, 2007·Proceedings of the National Academy of Sciences of the United States of America·Piero DalerbaMichael F Clarke
Jun 16, 2007·Gastroenterology·Stephanie MaXin-Yuan Guan
Feb 5, 2008·Cancer Cell·Zhen Fan YangSheung Tat Fan
Mar 6, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Emilia FransveaGianluigi Giannelli
Mar 6, 2009·Nature Reviews. Cancer·Kornelia Polyak, Robert A Weinberg
Mar 12, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yukiharu HiyoshiHideo Baba
Oct 13, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Muh-Hwa YangJaw-Ching Wu
Dec 1, 2009·Cell·Jean Paul ThieryM Angela Nieto
May 25, 2010·Nature Reviews. Cancer·Hiroaki Ikushima, Kohei Miyazono
Aug 11, 2010·The Journal of Clinical Investigation·Naotsugu HaraguchiMasaki Mori
Sep 8, 2010·Nature Cell Biology·Muh-Hwa YangKou-Juey Wu
Nov 3, 2010·Annals of Surgical Oncology·Hirohisa OkabeHideo Baba
Mar 10, 2011·Nature Medicine·Hans Clevers
Mar 26, 2011·Science·Christine L Chaffer, Robert A Weinberg
Oct 14, 2011·The New England Journal of Medicine·Hashem B El-Serag

❮ Previous
Next ❯

Citations

May 3, 2013·The Journal of Clinical Investigation·Taro Yamashita, Xin Wei Wang
Mar 22, 2014·Journal of Cancer Research and Clinical Oncology·Shuai HuGuoqiang Li
Nov 3, 2012·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Ching-Yu YenHsueh-Wei Chang
Mar 18, 2016·Journal of Clinical Medicine·Isabel FabregatJitka Soukupova
Jun 5, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Xianteng WangYongyu Shi
Jun 28, 2014·BioMed Research International·Ying-Erh ChouTzy-Yen Chen
Aug 15, 2015·Cancer Letters·Zhuo ChengJin Ding
Aug 19, 2016·British Journal of Cancer·Claudia BellomoAristidis Moustakas
Apr 20, 2013·Experimental Biology and Medicine·Karin WilliamsSusan Kasper
Dec 8, 2014·Experimental and Molecular Pathology·Shizuka KiuchiMasanori Kasahara
Feb 1, 2017·Molecular Cancer·Kouki NioShuichi Kaneko
Jun 17, 2015·International Journal of Cancer. Journal International Du Cancer·Bogdan-Tiberius PrecaMarc P Stemmler
Aug 5, 2015·International Journal of Cancer. Journal International Du Cancer·Keisuke KosumiHideo Baba
Jan 30, 2019·Genes & Development·Honghong ZhangChonghui Cheng
Feb 12, 2019·Journal of Cellular Physiology·Maryam AkbarzadehNasser Samadi
Jul 24, 2013·Journal of Gastroenterology and Hepatology·Hongyang Wang, Lei Chen
Jul 24, 2014·International Journal of Cancer. Journal International Du Cancer·Joan FernandoIsabel Fabregat
Mar 19, 2020·Cancers·Lucas-Alexander SchultePatrick C Hermann

❮ Previous
Next ❯

Related Concepts

Related Feeds

Carcinoma, Hepatocellular

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

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Cadherins and Catenins

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.

© 2021 Meta ULC. All rights reserved