Forkhead Box Transcription Factors: Double-Edged Swords in Cancer

Abstract

A plethora of treatment options exist for cancer therapeutics, but many are limited by side effects and either intrinsic or acquired resistance. The need for more effective targeted cancer treatment has led to the focus on forkhead box transcription factors as possible drug targets. Forkhead factors such as FOXA1 and FOXM1 are involved in hormone regulation, immune system modulation, and disease progression through their regulation of the epithelial-mesenchymal transition. Forkhead factors can influence cancer development, progression, metastasis, and drug resistance. In this review, we discuss the various roles of forkhead factors in biological processes that support cancer as well as their function as pioneering factors and their potential as targetable transcription factors in the fight against cancer.

Sestrin2 mediates FOXM1 expression to block the EMT process in non-small cell lung cancer through the AMPK/YAP pathway

“…FOXM1 is a member of Forkhead box transcription factors which widely engaged in various pathological processes such as EMT [37]. Massive evidences have demonstrated FOXM1 was a cancerogenic element in multifarious tumors including colon cancer, NSCLC [38,39].…”

CD147 promotes cisplatin resistance in ovarian cancer by inhibiting FOXM1 degradation via PI3k/Akt-GSK3β pathway

“…FOXM1 is critical in high-grade ovarian cancer and participates in a number of pathophysiological processes via activating the transcriptional expression of downstream molecules, including cell proliferation, cell cycle, cell differentiation, cell apoptosis ,invasion, angiogenesis, and DNA damage repair, etc. [23] [24] [25,26].…”

The DEAD-box protein p68 and β-catenin: the crucial regulators of FOXM1 gene expression in arbitrating colorectal cancer

“…Thus, a comprehensive analysis of signaling cross-talks and molecular players that trigger its initiation and progression is required. FOXM1 is found to be aberrantly overexpressed in multiple cancers through higher rates of proliferation, metastasis, influences tumor initiation and progression 21 . Furthermore, FOXM1 has been hailed as a potential molecular marker in CRC 15,19 .…”

“…However, a lot remains to be explored regarding the mechanisms of FOXM1 gene regulation. p68 acts as a coactivator of β-catenin 20 in several cancer types whereas a cross-talk between the Wnt/β-catenin pathway and FoxM1 has been reported in glioma stem cells 21–24 . Therefore, we sought to investigate the role of p68 and Wnt/β-catenin in the regulation of the FOXM1 gene expression in CRC and delineate the mechanistic details of this synergism.…”