PBX1-promoted SFRP4 transcription inhibits cell proliferation and epithelial-mesenchymal transition in endometrial carcinoma

The cell-biological program termed the epithelial-to-mesenchymal transition (EMT) plays an important role in both development and cancer progression. Depending on the contextual signals and intracellular gene circuits of a particular cell, this program can drive fully epithelial cells to enter into a series of phenotypic states arrayed along the epithelial-mesenchymal phenotypic axis. These cell states display distinctive cellular characteristics, including stemness, invasiveness, drug-resistance and the ability to form metastases at distant organs, and thereby contribute to cancer metastasis and relapse. Currently we still lack a coherent overview of the molecular and biochemical mechanisms inducing cells to enter various states along the epithelial-mesenchymal phenotypic spectrum. An improved understanding of the dynamic and plastic nature of the EMT program has the potential to yield novel therapies targeting this cellular program that may aid in the management of high-grade malignancies.

Endometrial cancer accounts for ~76,000 deaths amongst women worldwide. Disease mortality and the increasing number of new diagnoses make endometrial cancer an important consideration in women’s health, particularly in industrialized countries, where the incidence of this tumor type is highest. Most endometrial cancers are carcinomas, with the remainder being sarcomas. Endometrial carcinomas can be classified into several histological subtypes including endometrioid, serous and clear cell carcinomas. Histological subtyping is currently routinely used to guide prognosis and treatment decisions for endometrial cancer patients, while ongoing studies are evaluating the potential clinical utility of molecular subtyping. In this review we summarize the over-arching molecular features of endometrial cancers and highlight recent studies assessing the potential clinical utility of specific molecular features for early detection, disease risk stratification, and directing the use of targeted therapies.