E2F transcription factors and digestive system malignancies: How much do we know?

Abstract

The E2F proteins comprise a family of 8 members that function as transcription factors. They are key targets of the retinoblastoma protein (RB) and were initially divided into groups of activators and repressors. Accumulating data suggest that there is no specific role for each individual E2F member. Instead, each E2F can exert a variety of cellular effects, some of which represent opposing ones. For instance, specific E2Fs can activate transcription and repression, promote or hamper cell proliferation, augment or inhibit apoptosis, all being dependent on the cellular context. This complexity reflects the importance that these transcription factors have on a cell’s fate. Thus, delineating the specific role for each E2F member in specific malignancies, although not easy, is a challenging and continuously pursued task, especially in view of potential E2F targeted therapies. Therefore, several reviews are continuously trying to evaluate available data on E2F status in various malignancies. Such reviews have attempted to reach a consensus, often in the simplistic form of oncogenes or tumor suppressor genes for the E2Fs. However they frequently miss spatial and temporal alterations of these factors during tumor development, which should also be considered in conjunction with the status of the regulatory networks that these factors participate in. In the current ‘‘Letter to the Editor’’, we comment on the flaws, misinterpretations and omissions in one such review article published recently in the World Journal of Gastroenterology regarding the role of E2Fs in digestive system malignancies.

Keywords: E2F, Hepatocellular carcinoma, Pancreatic ductal adenocarcinoma, Gastrointestinal tract, Digestive system, p53, p73, Cancer, Apoptosis, Proliferation

Core tip: The roles of the E2F transcription factors can vary significantly in malignancies of the digestive system, often dictating different outcomes in separate compartments of the gastrointestinal tract. Knowledge of the molecular status of the regulatory networks that E2Fs participate in is imperative to define their role. Therefore the use of proper molecular analysis to investigate these networks, complemented also by functional analysis in cellular and animal models, is essential. All in all, such an approach can define chronologically and provide a wider and more accurate view on the exact roles that E2Fs may exhibit in the development of specific digestive system malignancies.