A comprehensive review of the roles of E2F1 in colon cancer

Abstract

E2F transcription factor 1 (E2F1) is a member of the E2F family of transcription factors. E2F1 binds to DNA with dimerization partner (DP) proteins through an E2 recognition site. The dissociation of E2F1 from retinoblastoma (Rb) protein recovers its transcriptional activity, which drives the cell cycle from the G1 to S phase. E2F1 has been shown to be involved in cellular proliferation, differentiation, and apoptosis in colon cancer. It was recently found that E2F1 also participates in the metastasis and chemoresistance of colon cancer. There are abundant experimental data regarding the actions of E2F1, which can be grouped as either pro-tumorigenic or pro-apoptotic. Despite a growing interest and plentiful data, there is currently no review that focuses on the role of E2F1 in colon cancer. Research on E2F1 and colon cancer has been scattered over various genes and microRNAs (miRNAs) that affect E2F1 expression. Here, we provide the first review that aims to consider and dissect all of the elucidated complex behaviors of E2F1 in colon cancer. This review also provides an analysis and conclusion regarding the current understanding of E2F1 in colon cancer in order to facilitate the direction of future research.

Keywords: E2F1; apoptosis; chemoresistance; colon cancer; proliferation.

Figure 1

Different actions of E2F1 and their corresponding target genes in CRC. E2F1 has been reported to play crucial roles in proliferation, chemoresistance, and apoptosis of CRC through activating different downstream effectors.

Figure 2

The regulatory mechanisms for E2F1 in CRC. E2F1 function in CRC is regulated at multiple levels including the transcriptional level (YB-1, NFY, and KRT23-induced transcription of the E2F1 gene), post-transcriptional level (E2F1 mRNA targeted by miR-362-3p, miR-17-92, and miR-526b-3p), post-translational level (deacetylation and acetylation of E2F1 protein exhibit opposite actions), protein-protein interaction level (dephosphorylated Rb sequesters E2F1 and hyper-phosphorylated Rb releases E2F1), and transcriptional activity level (XIAP, CIAP, and DP1 enhance the transcriptional activity of E2F1 protein). Arrowhead: promotion; Cycle: inhibition; Dashed line: indirect regulation.