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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.