An Update on the Potential Roles of E2F Family Members in Colorectal Cancer

Abstract

Colorectal cancer (CRC) is a major health burden worldwide, and thus, optimised diagnosis and treatments are imperative. E2F transcription factors (E2Fs) are a family of transcription factors consisting of eight genes, contributing to the oncogenesis and development of CRC. Importantly, E2Fs control not only the cell cycle but also apoptosis, senescence, DNA damage response, and drug resistance by interacting with multiple signaling pathways. However, the specific functions and intricate machinery of these eight E2Fs in human CRC remain unclear in many respects. Evidence on E2Fs and CRC has been scattered on the related regulatory genes, microRNAs (miRNAs), and competing endogenous RNAs (ceRNAs). Accordingly, some drugs targeting E2Fs have been transferred from preclinical to clinical application. Herein, we have systemically reviewed the current literature on the roles of various E2Fs in CRC with the purpose of providing possible clinical implications for patient diagnosis and prognosis and future treatment strategy design, thereby furthering the understanding of the E2Fs.

E2F3 gene expression is a potential negative prognostic marker for localised and MYCN not‐amplified neuroblastoma: Results of in silico analysis of 786 samples

“…E2F3 has been demonstrated to be a potential target for therapeutic drugs in other malignancies, and it is downregulated by chemotherapy agents, both alone or in combination with other drugs or with natural bioactive compounds. [58][59][60] Accordingly, the identification of suitable targets, associated to the E2F3 pathway, is advisable for future therapeutic interventions in patients with NB.…”

“…In conclusion, the results here presented point out the negative prognostic role of E2F3 in NB without amplification of MYCN , and suggest that these patients with augmented expression of E2F3 might be classified as intermediate risk. E2F3 has been demonstrated to be a potential target for therapeutic drugs in other malignancies, and it is downregulated by chemotherapy agents, both alone or in combination with other drugs or with natural bioactive compounds 58–60 . Accordingly, the identification of suitable targets, associated to the E2F3 pathway, is advisable for future therapeutic interventions in patients with NB.…”

E2F1 promotes cell cycle progression by stabilizing spindle fiber in colorectal cancer cells

“…E2F transcription factors (E2Fs) can activate or silence many oncogenes or tumor suppressor genes in various malignancies, which have been shown to be involved in cellular proliferation, differentiation, apoptosis, metastasis, and chemoresistance in colorectal cancer [ 5 , 6 ]. As the first member discovered, E2F1 is a transcription co-factor that interacts with retinoblastoma protein (RB) to regulate the transcription of cell cycle-related proteins [ 6 ].…”

“…E2F transcription factors (E2Fs) can activate or silence many oncogenes or tumor suppressor genes in various malignancies, which have been shown to be involved in cellular proliferation, differentiation, apoptosis, metastasis, and chemoresistance in colorectal cancer [ 5 , 6 ]. As the first member discovered, E2F1 is a transcription co-factor that interacts with retinoblastoma protein (RB) to regulate the transcription of cell cycle-related proteins [ 6 ]. The cyclin dependent kinase 4 (CDK4)-pRB-E2F1 axis has been shown to be essential for cell cycle progression in normal and cancer cells, and high expression of E2F1 has been found to promote the proliferation of cancer cells by transactivating cell cycle-related kinases [ 7 , 8 ].…”

High Expression of E2F4 Is an Adverse Prognostic Factor and Related to Immune Infiltration in Oral Squamous Cell Carcinoma

“…Nine members of the family are located on different chromosomes and subdivided into activators (E2F1, E2F2, and E2F3a) and repressors (E2F3b, E2F4, E2F5, E2F6, E2F7, and E2F8) based on detail functions [5]. Abnormal expression of some E2F family transcription factors has been found in numerous human malignancies including ovarian [6], gastric [7], and colorectal cancer [8]. E2Fs are also supposed to have complex and distinct roles in OSCC.…”