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.
Highlights
In recent years, a number of FOX family members have been linked to tumorigenesis, carcinogenesis, and the survival of malignant cell growth [1, 2]
Han et al, 2015 found that forkhead box C1 (FOXC1) interacts with Gli2 in different basal-like breast cancer (BLBC) cell lines through direct binding, and that FOXC1 mediates the non-canonical Smoothened (SMO)-Independent Hedgehog (Hh) signaling that establishes the BLBC stem-like phenotype and antiHh sensitivity (Figure 3) [7]. These findings clearly suggest that FOXC1 is a specific biomarker for BLBC
A rescue experiment involving the overexpression of FOXC1 abrogated miRNA 495 (miR495)’s inhibition of cell growth and migration as well as promotion of apoptosis in AN3CA and KLE cells [29]. These findings provide a strong argument for FOXC1’s role as a target of miR495 in the miR495-regulated malignancy phenotype found in endometrial cancer
Summary
A number of FOX family members have been linked to tumorigenesis, carcinogenesis, and the survival of malignant cell growth [1, 2]. While FOXC1 missense mutations that are associated with ARS usually reduce gene activity, increased FOXC1 function appears to be often linked to more aggressive cancer phenotypes in BLBC, HCC, HL, and NHL.
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