Angiotensin receptor blockade attenuates cholangiocarcinoma cell growth by inhibiting the oncogenic activity of Yes-associated protein.

Cancer Letters
Soichiro SaikawaHitoshi Yoshiji

Abstract

Cholangiocarcinoma (CCA) is a destructive malignancy with limited responsiveness to conventional chemotherapy. Although angiotensin receptor blockers (ARBs) have gained attention for their potential anticancer activity, little is known about their effects on CCA. The transcriptional co-activator, Yes-associated protein (YAP) is a critical oncogene in several cancers, including CCA. Following recent evidence showing that YAP is regulated by angiotensin II (AT-II), we investigated the effects of an ARB, losartan, on two human CCA cell lines (KKU-M213 and HuCCT-1) with regards to YAP oncogenic regulation. Losartan suppressed AT-II-induced CCA cell proliferation in a dose-dependent manner, induced apoptosis, decreased YAP (Ser127), and downregulated the YAP target genes CTGF, CYR61, ANKRD1, and MFAP5. However, losartan did not affect epithelial-mesenchymal transition, differentiation, or stemness in the CCA cells. Xenograft tumor growth assay showed that oral administration of a low clinical dose of losartan considerably reduced subcutaneous tumor burden and attenuated intratumor vascularization in CCA cell-derived xenograft tumors in BALB/c nude mice. These results indicate that ARB therapy could serve as a potential novel strateg...Continue Reading

References

Jul 4, 2003·The Journal of Clinical Investigation·Kimiyasu EgamiTsutomu Imaizumi
Aug 3, 2005·Trends in Endocrinology and Metabolism : TEM·Frédérique Deshayes, Clara Nahmias
Sep 27, 2005·Physiological Reviews·Nina Wettschureck, Stefan Offermanns
Apr 9, 2008·Reproduction : the Official Journal of the Society for the Study of Fertility·D HerrC Wulff
May 3, 2008·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Hidenori ItabashiTomoyuki Masuda
Dec 30, 2008·Molecular Cell·Eleonora LapiGiovanni Blandino
Jun 3, 2009·Proceedings of the National Academy of Sciences of the United States of America·Daniel R RhodesArul M Chinnaiyan
Apr 9, 2010·The New England Journal of Medicine·Juan ValleUNKNOWN ABC-02 Trial Investigators
Mar 8, 2013·Nature Reviews. Cancer·Kieran F HarveyDavid M Thomas
May 16, 2014·EMBO Reports·Jung-Soon MoKun-Liang Guan
Aug 26, 2014·Matrix Biology : Journal of the International Society for Matrix Biology·Alison MiyamotoGregory Hogrebe
Dec 11, 2014·Acta Biochimica Et Biophysica Sinica·Xin ZhouQun-Ying Lei
Mar 10, 2015·Nature Cell Biology·Jung-Soon MoKun-Liang Guan
May 13, 2015·Nature Communications·Hyun-Jung ChoiYoung-Guen Kwon
May 28, 2015·Oncotarget·Tiemin PeiLianxin Liu
Jul 16, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Patricia MartiJan S Tchorz
Aug 16, 2015·Cell·Hyun Woo ParkKun-Liang Guan
Jan 31, 2016·The Journal of Biological Chemistry·Sumera RizviGregory J Gores
Jun 15, 2016·Cancer Cell·Francesca ZanconatoStefano Piccolo
Jun 27, 2017·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Takanobu TakezakoKoichi Node
Aug 15, 2017·The Journal of Clinical Investigation·Jongshin KimGou Young Koh
Oct 11, 2017·Nature Reviews. Clinical Oncology·Sumera RizviGregory J Gores

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Citations

May 11, 2019·Cells·Jiaqian Luo, Fa-Xing Yu
Dec 12, 2018·Journal of Cellular Physiology·Ning ShengShaohua Fan
Jun 14, 2019·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Z ChenH Kang
Dec 2, 2018·Journal of Oncology·Maiko Matsushita, Mai Kawaguchi
Nov 26, 2020·Annual Review of Pathology·Jordan H Driskill, Duojia Pan
Jan 11, 2021·Journal of Experimental & Clinical Cancer Research : CR·Piera TocciAnna Bagnato
Nov 6, 2018·Life Sciences·Haojun XieYuanxiong Cheng
Jun 8, 2021·Frontiers in Oncology·José A Carlos-EscalanteTalia Wegman-Ostrosky
Dec 3, 2021·Biological & Pharmaceutical Bulletin·Yoshie TsujiyaNoboru Okamura

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