Cyclin E: a potential treatment target to reverse cancer chemoresistance by regulating the cell cycle.

Abstract

The cyclin family plays important roles in regulating the proliferative cycle of mammalian cells. Among the members of this family, cyclin E regulates multiple downstream molecules, such as the retinoblastoma susceptibility gene (RB1) and the transcription factor E2F, by interacting with cyclin-dependent kinases (CDKs) and plays an important role in the cell cycle transition from G1 to S phase. Over the years, studies have shown that cyclin E is closely related to the chemotherapy resistance of tumor cells and that its expression in tumor cells is closely related to prognosis. The dysregulated expression of cyclin E has a definite effect not only on the cell cycle regulation of tumor cells but also on the presence of low-molecular-weight cyclin E (LMW-E) and other cyclins that render tumor cells resistant. In addition, many studies in recent years have confirmed that chemotherapy resistance mediated by cyclin E can be reversed. For example, the combination of a cyclin-dependent kinase inhibitor (CKI) with anticancer drugs or the therapeutic targeting of related genes improves chemotherapy resistance by reducing the level or activity of cyclin E in tumor cells. This review summarizes the specific processes by which cyclin E regulates the cell cycle, its relationship to chemotherapy resistance in cancer, and its potential as a clinical therapeutic target to reverse chemotherapy resistance.