Targeting signal-transducer-and-activator-of-transcription 3 sensitizes human cutaneous melanoma cells to BRAF inhibitor

Cancer Biomarkers : Section a of Disease Markers
Xiaohui WangLinxia Zhang

Abstract

Melanoma treatment with the BRAF V600E inhibitor vemurafenib provides therapeutic benefits but the common emergence of drug resistance remains a challenge. To define molecular mechanisms of vemurafenib resistance, we generated A375-R, WM35-R cell lines resistant to vemurafenib and show that the phosphorylated (p)-STAT3 was upregulated in these cells in vitro and in vivo. In particular, activation of the Signal-transducer-and-activator-of-transcription 3 (STAT3) pathway was associated with vemurafenib resistance. Inhibition of this pathway with STAT3-specific siRNA (shRNA) sensitized A375-R, WM35-R cells to vemurafenib and induced apoptosis in vitro and in vivo. Moreover, targeting STAT3 induced expression of miR-579-3p and elicited resistance to vemurafenib. However, targeting microRNA (miR)-579-3p with anti-miR-579-3p reversed the resistance to vemurafenib. Together, these results indicated that STAT3-mediated downexpression of miR-579-3p caused resistance to vemurafenib. Our findings suggest novel approaches to overcome resistance to vemurafenib by combining vemurafenib with STAT3 sliencing or miR-579-3p overexpression.

References

Jun 18, 2002·Nature·Helen DaviesP Andrew Futreal
Feb 18, 2004·Nature Reviews. Cancer·Hua Yu, Richard Jove
Sep 3, 2004·The New England Journal of Medicine·Hensin TsaoArthur J Sober
Jun 7, 2005·Nature Medicine·James E Darnell
May 15, 2010·Cancer Gene Therapy·J MaC Ji
Sep 8, 2010·The New England Journal of Medicine·Keith T FlahertyPaul B Chapman
Mar 9, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Nikhil WagleLevi A Garraway
Jun 7, 2011·The New England Journal of Medicine·Paul B ChapmanUNKNOWN BRIM-3 Study Group
Jan 25, 2013·The Journal of Investigative Dermatology·Fang LiuRutao Cui
May 30, 2013·The Oncologist·Michael A PostowRichard D Carvajal
Oct 18, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hemant K BidPeter J Houghton
Mar 13, 2014·Archives of Dermatological Research·Andrew MamalisJared Jagdeo
Jun 25, 2014·Nature Reviews. Cancer·Matthew HolderfieldMartin McMahon
Sep 1, 2013·EJC Supplements : EJC : Official Journal of EORTC, European Organization for Research and Treatment of Cancer ... [et Al.]·John B A G Haanen
Aug 6, 2016·Oncotarget·Jahangir AbdiHong Chang
Aug 10, 2016·Proceedings of the National Academy of Sciences of the United States of America·Luigi FattoreGennaro Ciliberto
Nov 30, 2016·BioFactors·Saeideh MomtazSeyed Mohammad Nabavi
Jan 6, 2017·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Jae-Hyeon KimMichael Lee
Jun 24, 2017·AAPS PharmSciTech·Anup JoseVenkata Vamsi Krishna Venuganti
Oct 6, 2017·Oncotarget·Xiaoyang LiZhenfeng Duan

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Citations

Sep 4, 2020·Pharmacological Reports : PR·Aliaa M MohassabMohamed Abdel-Aziz
May 26, 2021·Scientific Reports·Roberto H BarbierWilliam D Figg

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