Role of the Forkhead box family protein FOXF2 in the progression of solid tumor: systematic review

Abstract

Background: FOXF2 was reported to involve in a variety of biological behaviors that include the development of the central nervous system, tissue homeostasis, epithelia-mesenchymal interactions, regulation of embryonic development, and organogenesis.

Purpose: Understanding how FOXF2 influences the growth and development of cancer could provide valuable insights for researchers to develop novel therapeutic strategies.

Results: In this review, we investigate the underlying impact of FOXF2 on tumor cells, including the transformation of cellular phenotype, capacity for migration, invasion, and proliferation, colonization of circulating cells, and formation of metastatic nodules. In addition, we discuss the molecular mechanisms of FOXF2 in different cancers, including hepatocellular, esophageal, breast, colon, lung, prostate gland, as well as its role in embryonic development.

Conclusion: FOXF2 is a gene encoding a forkhead transcription factor belonging to the Forkhead Box family. The protein functions by recruiting activation transcription factors and basic components to activate the transcription of genes that interact with the complex. This review provides an in-depth analysis of the FOXF2's function and pleiotropic roles in cancer development and progression.

Keywords: Cancer; Cancer development; Cancer progression; FOX2; Signal pathway.

Fig. 1

The signaling pathway of FOXF2 in tumor progression. TGFβ receptor activates and induces the receptor-bound SMADS phosphorylation followed by subsequent SMAD complex formation. The SMAD complex activates FOXF2 expression with the transcription of EGFR ligands betacellulin (BTC) and amphiregulin (ATEG) repression. FOXF2 also transcriptionally activates NOXA (proapoptotic gene) and induces the caspase-dependent apoptosis. FOXF2 could downregulate the E-cadherin through upregulating ZEB1/ZEB2 and downregulating ID2, affecting the motility of cells. FOXF2 upregulates E3 ligase IRF2BPL and induces β-catenin ubiquitination and degradation. FOXF2 can downregulate the transcription of TCF/LEF. Air pollution can induce DbA upregulation and consequently induced up-regulation of CAR10 and EGFR through FOXF2-YB-1 signal cascade. (Biorender licence number: EH27E0WTW0)