FOXC1, the new player in the cancer sandbox

// Fahed A. Elian 1 , Elizabeth Yan 1 and Michael A. Walter 1 1 Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada Correspondence to: Michael A. Walter, email: mwalter@ualberta.ca Keywords: transcription factor; breast cancer; basal-like Received: September 21, 2017      Accepted: October 28, 2017      Published: November 28, 2017 ABSTRACT In recent years, rapidly accumulating evidence implicates forkhead box C1 ( FOXC1 ) in cancer, especially in studies of basal-like breast cancer (BLBC). Other studies have followed suit, demonstrating that FOXC1 is not only a major player in this breast cancer subtype, but also in hepatocellular carcinoma (HCC), endometrial cancer, Hodgkin’s lymphoma (HL), and non-Hodgkin’s lymphoma (NHL). The FOXC1 gene encodes a transcription factor that is crucial to mesodermal, neural crest, and ocular development, and mutations found in FOXC1 have been found to cause dominantly inherited Axenfeld-Rieger Syndrome (ARS). Interestingly, while FOXC1 missense mutations that are associated with ARS usually reduce gene activity, increased FOXC1 function now appears to be often linked to more aggressive cancer phenotypes in BLBC, HCC, HL, and NHL. This review discusses not only the role of FOXC1 in cancer cell progression, proliferation, differentiation, and metastasis, but also the underlying mechanisms of how FOXC1 can contribute to aggressive cancer phenotypes.