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

详细信息    查看全文

• 作者：Caixia Ren^a ; ^b ; ^c ; Juan Du^a ; ^b ; ^c ; Chenguang Xi^d ; Yu Yu^a ; ^b ; ^c ; Ajin Hu^d ; Jun Zhan^a ; ^b ; ^c ; Hongyan Guo^e ; Weigang Fang^a ; ^d ; Congrong Liu^d ; ^{congrong_liu@hsc.pku.edu.cn" class="auth_mail} ; Hongquan Zhang^a ; ^b ; ^c ; ^{Hongquan.Zhang@bjmu.edu.cn" class="auth_mail}
• 关键词：Serous epithelial ovarian cancer ; Kindlin-2 ; E-cadherin ; Estrogen receptor 伪
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：28 March, 2014
• 年：2014
• 卷：446
• 期：1
• 页码：187-194
• 全文大小：2200 K

文摘

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 伪 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.