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Kindlin-2 inhibits serous epithelial ovarian cancer peritoneal dissemination and predicts patient outcomes

Ren, Caixia, Du, Juan, Xi, Chenguang, Yu, Yu, Hu, Ajin, Zhan, Jun, Guo, Hongyan, Fang, Weigang, Liu, Congrong, Zhang, Hongquan
Biochemical and biophysical research communications 2014 v.446 pp. 187-194
animal models, animal ovaries, cadherins, disease course, epithelium, estrogen receptors, gene expression regulation, neoplasm cells, ovarian neoplasms, patients, risk factors, signal transduction
Kindlin-2 has been known to promote most cancer progression through regulation of multiple signaling pathways. However, a novel tumor suppressive role of Kindlin-2 was identified in serous epithelial ovarian cancer progression, which sharply contrasts to the tumor promoting roles for Kindlin-2 in most other cancers. While we demonstrated that Kindlin-2 was highly expressed in control tissues, a drastic low expression of Kindlin-2 was found in the tumor tissues of serous epithelial ovarian cancer, especially in the high-grade serous epithelial ovarian cancer. Importantly, Kindlin-2 inhibited serous epithelial ovarian cancer cell peritoneal dissemination in a mouse model. For clinical relevance, low Kindlin-2 expression correlated with higher tumor grade and older patients. Intriguingly, decreased Kindlin-2 expression predicts poor overall and progression-free survivals in serous epithelial ovarian cancer patients. Mechanistically, Kindlin-2 induced a mesenchymal to epithelial transition in serous epithelial ovarian cancer cells, at least in part, by up-regulation of estrogen receptor α which was recruited to the promoter of E-cadherin and thereby enhanced the transcription of E-cadherin. Collectively, we concluded that inadequate Kindlin-2 is an independent risk factor for serous epithelial ovarian cancer patients.