S100A4/non-muscle myosin IIA/p53 axis contributes to aggressive features in ovarian high-grade serous carcinoma.

S100A4/non-muscle myosin IIA/p53 axis contributes to aggressive features in ovarian high-grade serous carcinoma. Am J Pathol. 2020 Aug 14;: Authors: Hiruta A, Oguri Y, Yokoi A, Matsumoto T, Oda Y, Tomohiro M, Hashimura M, Jiang Z, Tochimoto M, Nakagawa M, Saegusa M Abstract S100A4 is a small calcium-binding protein that exerts its biological functions by interacting with non-muscle myosin IIA (NMIIA) and p53. Although S100A4 promotes metastasis in several tumors, little is known about its involvement in the progression of ovarian high-grade serous carcinomas (HGSC). Herein, we focused on functional roles of the S100A4/NMIIA/p53 axis in these tumors. In HGSC cell lines harboring mutant p53 (p53mt), knockdown (KD) of S100A4 reduced the expression of several epithelial-mesenchymal transition (EMT) /cancer stem cell (CSC) markers and the ALDH1high population, consistent with an inhibition of 'stemness' features. S100A4-KD also increased apoptosis, decreased cell proliferation, and accelerated cell mobility. This was accompanied by increased Snail expression, which in turn was likely due to loss of p53 function. In contrast, specific inhibition of NMIIA by blebbistatin induced phenotypes that -with the exception of cell proliferation and mobility- were opposite to those observed in S100A4-KD cells. In clinical samples, cytoplasmic and/or nuclear interactions between S100A4, NMIIA, and p53mt were observed. In addition, high expression of S...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research