EMP2 is a novel therapeutic target for endometrial cancer stem cells

Abstract

Previous studies have suggested that overexpression of the oncogenic protein epithelial membrane protein-2 (EMP2) correlates with endometrial carcinoma progression and ultimately poor survival from disease. To understand the role of EMP2 in the etiology of disease, gene analysis was performed to show transcripts that are reciprocally regulated by EMP2 levels. In particular, EMP2 expression correlates with and helps regulate the expression of several cancer stem cell associated markers including aldehyde dehydrogenase 1 (ALDH1). ALDH expression significantly promotes tumor initiation and correlates with the levels of EMP2 expression in both patient samples and tumor cell lines. As therapy against CSCs in endometrial cancer is lacking, the ability of anti-EMP2 IgG1 therapy to reduce primary and secondary tumor formation using xenograft HEC1A models was determined. Anti-EMP2 IgG1 reduced the expression and activity of ALDH and correspondingly reduced both primary and secondary tumor load. Our results collectively suggest that anti-EMP2 therapy may be a novel method of reducing endometrial cancer stem cells.

Targeting Endometrial Cancer Stem Cell Activity with Metformin Is Inhibited by Patient-Derived Adipocyte-Secreted Factors

“…The proportions of ALDH high and CD133 +ve cells in the two endometrial cancer cell lines reported here are similar to those in other studies [40,41,42]. This is the first study, however, in which the two populations of cells with cancer stem cell activity have been directly compared at a functional and genetic level.…”

Targeting endometrial cancer stem cell activity with metformin is inhibited by patient-derived adipocyte-secreted factors

“…The proportions of ALDH high and CD133 +ve cells in the two endometrial cancer cell lines reported here are similar to those in other studies (42)(43)(44). This is the first study, however, in which the two populations of cells with cancer stem cell activity have been directly compared at a functional and genetic level.…”

Integrated Analysis of MicroRNA (miRNA) and mRNA Profiles Reveals Reduced Correlation between MicroRNA and Target Gene in Cancer

“…Moreover, 38 critical genes in BRCA and 15 critical genes in KICH were significantly enriched in cell division ( p = 6.29E-08, Bonferroni correction) and DNA replication cell proliferation ( p = 5.40E-04, Bonferroni correction). The dysregulated miRNA-target gene pairs involved in these genes like miR-215/ SKA1 , miR-3653/ EMP2 and miR-192/ PIM1 , might enable the cells to evade normal constraints on cell proliferation [45–47].…”