Nuclear ESM1 promotes prostate cancer stemness through β-catenin signaling

Abberant expression and protein localization of ESM1 were found in prostate cancer. The high expression of ESM1 is associated with prostate cancer stemness and progression. Thus, ESM1 is clinically relevant to poor overall survival and metastasis. However, the molecular mechanisms by which ESM1 contribute to prostate cancer is not yet understood. To discover the role of ESM1 mislocalization in prostate cancer, RNA-seq analysis was performed on 22Rv1 cells overexpressing with different ESM1. Our study demonstrate that nuclear ESM1 may support prostate cancer stemness by interacting with the ARM domain of β-catenin to stabilize β-catenin-Tcf4 complex and facilitate the transactivation of Wnt/β-catenin signaling targets. Our results establish the significance of ESM1 in driving metastasis in prostate cancer by coordinating the Wnt/β-catenin pathway, with implication for its potential use as a diagnostic or prognostic biomarker and as a candidate therapeutic target in prostate cancer. RNA-seq of ESM1-overexpressing prostate cancer cells (22Rv1). We have two vector groups which are different controls to overexpression group. Vector-1 is the control for ESM1 group while Vector-2 is control of ESM1-NLS and ESM1-NES group.