Opposing Roles of the Forkhead Box Factors FoxM1 and FoxA2 in Liver Cancer

Molecular Cancer Research : MCR
Vaibhav ChandPradip Raychaudhuri

Abstract

The forkhead box transcription factor FoxM1 is essential for hepatocellular carcinoma (HCC) development, and its overexpression coincides with poor prognosis. Here, we show that the mechanisms by which FoxM1 drives HCC progression involve overcoming the inhibitory effects of the liver differentiation gene FoxA2. First, the expression patterns of FoxM1 and FoxA2 in human HCC are opposite. We show that FoxM1 represses expression of FoxA2 in G1 phase. Repression of FoxA2 in G1 phase is important, as it is capable of inhibiting expression of the pluripotency genes that are expressed mainly in S-G2 phases. Using a transgenic mouse model for oncogenic Ras-driven HCC, we provide genetic evidence for a repression of FoxA2 by FoxM1. Conversely, FoxA2 inhibits expression of FoxM1 and inhibits FoxM1-induced tumorigenicity. Also, FoxA2 inhibits Ras-induced HCC progression that involves FoxM1. IMPLICATIONS: The observations provide strong genetic evidence for an opposing role of FoxM1 and FoxA2 in HCC progression. Moreover, FoxM1 drives high-grade HCC progression partly by inhibiting the hepatocyte differentiation gene FoxA2.

References

Sep 8, 1995·Science·R KühnK Rajewsky
Jun 17, 2005·Nature·Catherine S LeeKlaus H Kaestner
Nov 7, 2007·The Journal of Biological Chemistry·Vladimir PetrovicAngela L Tyner
Nov 21, 2007·Biological Chemistry·Inken Wierstra, Jürgen Alves
Feb 22, 2008·CA: a Cancer Journal for Clinicians·Ahmedin JemalMichael J Thun
Nov 7, 2008·Journal of Hepato-biliary-pancreatic Surgery·Toshiro MasudaHideo Baba
May 5, 2009·Cell Cycle·Marianna Halasi, Andrei L Gartel
Aug 22, 2009·The EMBO Journal·Hyun Jung ParkPradip Raychaudhuri
Mar 17, 2010·Oncogene·W-L Tsai, R T Chung
Jul 30, 2010·Current Medical Research and Opinion·A SanyalV Barghout
Aug 3, 2010·World Journal of Gastroenterology : WJG·Wojciech BlonskiKimberly A Forde
Jan 5, 2011·EMBO Molecular Medicine·Hyun Jung ParkPradip Raychaudhuri
Feb 8, 2011·CA: a Cancer Journal for Clinicians·Ahmedin JemalDavid Forman
Apr 22, 2011·Cancer Research·Zebin WangPradip Raychaudhuri
Jun 30, 2011·Cancer Research·Pradip Raychaudhuri, Hyun Jung Park
Oct 29, 2011·American Journal of Respiratory Cell and Molecular Biology·Aarti RaghavanJ Usha Raj
Jul 21, 2012·Cell Reports·Janai R CarrPradip Raychaudhuri
Nov 10, 2012·Cancer Research·Aihua Gong, Suyun Huang
Jul 30, 2014·Seminars in Cancer Biology·Laura BellaEric W-F Lam
Aug 2, 2015·Cell·Kevin Andrew Uy GonzalesHuck-Hui Ng
Oct 5, 2014·Bio-protocol·Kristina Y Aguilera, Rolf A Brekken
Apr 8, 2017·Scientific Reports·Nishit K MukhopadhyayPradip Raychaudhuri

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