Hyaluronan-mediated motility receptor confers resistance to chemotherapy via TGFβ/Smad2-induced epithelial-mesenchymal transition in gastric cancer

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Huizhong ZhangDongsheng Zhang

Abstract

Chemotherapy is one of the vital treatments for gastric cancer (GC) patients, especially those suffering advanced stages. Chemoresistance results in tumor relapse, leading to poor prognosis in GC patients; thus, identifying key regulators in this process might provide novel clues for GC therapy. Herein, we identify hyaluronan-mediated motility receptor (HMMR) as a key regulator of chemoresistance in GC. HMMR was found to be substantially up-regulated in 5-fluorouracil (5-Fu)-resistant GC biopsies and cell lines. High expression of HMMR significantly correlates with tumor relapse and predicts poorer prognosis in GC patients. Moreover, we observed that HMMR induced epithelial-mesenchymal transition and increased the cancer stem cell properties of GC, thus rendering resistance to chemotherapy. Importantly, silencing of HMMR effectively increased the susceptibility to 5-Fu therapy both in vitro and in vivo. Furthermore, we demonstrated that HMMR activates the TGF-β/Smad2 signaling pathway, which was required for the HMMR-mediated oncogenic effects and exhibited significant clinical relevance with HMMR expression. These findings reveal a critical role for HMMR in the chemoresistance of GC and suggest that HMMR might be a potential p...Continue Reading

References

Jan 18, 2002·The New England Journal of Medicine·Iype AbrahamRaaj K Praseedom
Aug 24, 2002·The Journal of Biological Chemistry·Masayuki FunabaLawrence S Mathews
Jun 26, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tomoko HayashidaH William Schnaper
Sep 29, 2006·The New England Journal of Medicine·Jaswinder SinghAshok K Malani
Jun 10, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Shigeo TakaishiTimothy C Wang
Jul 30, 2008·Cell·Joan Massagué
May 6, 2009·Stem Cells·Shigeo TakaishiTimothy C Wang
Sep 3, 2009·Neoplasia : an International Journal for Oncology Research·Kilian M GustMark Ringhoffer
May 5, 2012·Seminars in Cancer Biology·Christina Scheel, Robert A Weinberg
Sep 25, 2012·Nature Reviews. Drug Discovery·Rosemary J Akhurst, Akiko Hata
Mar 4, 2014·World Journal of Gastroenterology : WJG·Michele OrdituraFerdinando De Vita
Apr 9, 2014·Cancer Research·Jessica TilghmanMingyao Ying
Jun 7, 2014·Molecular Cell·Hariharan EaswaranStephen B Baylin
Aug 27, 2014·BioMed Research International·Cornelia TolgEva A Turley
Oct 16, 2014·Stem Cell Reports·Juli J UnternaehrerGeorge Q Daley
Apr 29, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Manish A Shah
Apr 30, 2015·Asian Pacific Journal of Cancer Prevention : APJCP·Zhen-Qin Qiu, Zhen-Rong Qiu
Oct 17, 2015·Expert Review of Gastroenterology & Hepatology·Tae-Yong KimYung-Jue Bang
Feb 13, 2016·Oncotarget·Alexandra SchützeKatharina Röck
Jun 5, 2016·Trends in Molecular Medicine·Simona Corso, Silvia Giordano
Sep 2, 2016·Chinese Journal of Cancer·Weijing Sun, Li Yan
Oct 25, 2016·Biochimica Et Biophysica Acta·Fang RenZhenfeng Duan
Nov 24, 2016·Cancer Metastasis Reviews·Christine L ChafferRobert A Weinberg
Jan 25, 2017·Cancer·Tanios Bekaii-Saab, Bassel El-Rayes
Feb 6, 2017·Continuum : Lifelong Learning in Neurology·Bart M Demaerschalk
Feb 12, 2017·Cell·Arthur W LambertRobert A Weinberg
Mar 5, 2017·Seminars in Cancer Biology·Claudia PeitzschAnna Dubrovska
Sep 29, 2017·Journal of Ovarian Research·Stephanie T ButtermorePatricia A Kruk
Mar 15, 2018·Journal of Cellular Biochemistry·Tulika MitraSib S Roy
Jun 13, 2018·Proceedings of the National Academy of Sciences of the United States of America·Yen-An TangQiang Yu

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Citations

Mar 3, 2020·Frontiers in Molecular Biosciences·Erik HenkeSüleyman Ergün
Aug 23, 2020·International Journal of Molecular Sciences·Jinfen WeiHongli Du
Sep 16, 2020·BMC Molecular and Cell Biology·Jianzhou LiuGary Guishan Xiao
Mar 22, 2021·The Journal of Biological Chemistry·Matías Arturo PibuelSilvina Laura Lompardía
Sep 4, 2021·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Kenichiro FurukawaKen Yamaguchi
Sep 18, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jun LuChang-Ming Huang

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