ENDOG Impacts on Tumor Cell Proliferation and Tumor Prognosis in the Context of PI3K/PTEN Pathway Status.

EndoG influences mitochondrial DNA replication and is involved in somatic cell proliferation. Here, we investigated the effect of expression on proliferation in different tumor models. Noteworthy, deficiency reduced proliferation of endometrial tumor cells expressing low PTEN/high -AKT levels, and deletion blunted the growth of PTEN-deficient 3D endometrial cultures. Furthermore, silencing reduced proliferation of follicular thyroid carcinoma and glioblastoma cell lines with high -AKT expression. High expression was associated with a short time to treatment in a cohort of patients with chronic lymphocytic leukemia (CLL), a B-cell lymphoid neoplasm with activation of PI3K/AKT. This clinical impact was observed in the less aggressive CLL subtype with mutated IGHV in which high and low levels were associated with worse outcome. In summary, our results show that reducing expression hinders growth of some tumors characterized by low PTEN activity and high -AKT expression and that has prognostic value for some cancer types.