Abstract
Hepatocyte nuclear factor 1 homeobox alpha (HNF1α) is a transcription factor involved in endodermal organogenesis and pancreatic precursor cell differentiation and development. Earlier studies have reported a role for HNF1α in pancreatic ductal adenocarcinoma (PDAC) but it is controversial. The mechanism by which it impacts PDAC is yet to be explored in depth. In this study, using the online databases we observed that HNF1α is upregulated in PDAC, which was also confirmed by our immunohistochemical analysis of PDAC tissue microarray. Silencing HNF1α reduced the proliferative, migratory, invasive and colony forming capabilities of pancreatic cancer cells. Key markers involved in these processes (pPI3K, pAKT, pERK, Bcl2, Zeb, Snail, Slug) were significantly changed in response to alterations in HNF1α expression. On the other hand, overexpression of HNF1α did not induce any significant change in the aggressiveness of pancreatic cancer cells. Our results demonstrate that reduced expression of HNF1α leads to inhibition of pancreatic cancer growth and progression, which indicates that it could be a potential oncogene and target for PDAC.
References
Dec 5, 1998·DNA and Cell Biology·B LinJ Y Chou
Nov 26, 2002·Oncogene·Riyaz N H ShahHelen C Hurst
Jul 16, 2003·The Journal of Biological Chemistry·Cécile HaumaitreSilvia Cereghini
Nov 20, 2009·PloS One·Lorna W HarriesAnna L Gloyn
Apr 27, 2010·Pancreas·Emily L DeerSean J Mulvihill
Jun 2, 2011·The Journal of Biological Chemistry·Caroline BonnerJochen H M Prehn
Feb 22, 2014·Nature Reviews. Molecular Cell Biology·Samy LamouilleRik Derynck
May 9, 2014·PloS One·Ramadevi SubramaniRajkumar Lakshmanaswamy
May 21, 2014·Cancer Research·Lola RahibLynn M Matrisian
Sep 23, 2014·Carcinogenesis·Jason W HoskinsLaufey T Amundadottir
Oct 11, 2014·Experimental & Molecular Medicine·Ramadevi SubramaniRajkumar Lakshmanaswamy
Mar 21, 2015·PloS One·Zhaofan LuoDonghui Li
Aug 21, 2015·The Journal of Biological Chemistry·Sachin S HajarnisPeter Igarashi
Feb 9, 2016·Nature Medicine·Elisa M NollMartin R Sprick
Mar 19, 2016·Oncotarget·Ramadevi SubramaniRajkumar Lakshmanaswamy
Mar 14, 2017·Cancer Cell International·Yang HuHua Tang
May 13, 2017·Current Medicinal Chemistry·Harald ManggeJohannes Haybaeck
Jul 22, 2017·Neoplasia : an International Journal for Oncology Research·Darshan S ChandrashekarSooryanarayana Varambally
Nov 5, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alexander MuckenhuberWilko Weichert
Jan 10, 2018·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Mar 16, 2018·Oncogenesis·Libing ShenWenyuan Wang
Jul 7, 2018·Oncogenesis·Ramadevi SubramaniRajkumar Lakshmanaswamy
Aug 4, 2018·ELife·Ethan V AbelDiane M Simeone
Jan 9, 2019·Experimental & Molecular Medicine·Arunkumar ArumugamRajkumar Lakshmanaswamy
Dec 8, 2019·Clinical Epigenetics·Yang HuHua Tang
Mar 23, 2020·Gastroenterology·Peter Storz, Howard C Crawford
Apr 21, 2020·Theranostics·Dan SuQuanbo Zhou