Qiu Zhaoyan, Chu Yi, Xu Bing, Wang Qian, Jiang Mingzuo, Li Xiaowei, Wang Gang, Yu Pengfei, Liu Guoxiao, Wang Hua, Kang Huijie, Liu Jiayu, Zhang Yu, Jin Jian-Ping, Wu Kaichun, Liang Jie
Department of General Surgery, Chinese PLA General Hospital, Beijing, China.
State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
Oncotarget. 2017 May 9;8(34):56428-56442. doi: 10.18632/oncotarget.17701. eCollection 2017 Aug 22.
Calponin 2 plays an important role in regulating actin cytoskeleton, which is critical for cell division and migration. Previous studies have demonstrated that calponin 2 inhibits prostate cancer cell proliferation and metastasis. However, the role of calponin 2 in pancreatic tumor growth, metastasis and patient survival remains unclear. Here, we demonstrate that the level of calponin 2 is a positive prognostic factor for patients with pancreatic ductal adenocarcinoma (PDAC). Patients with high calponin 2 expression in the tumor presented less lymph node metastasis and longer survival. Knockdown of calponin 2 facilitated pancreatic cancer cell proliferation and metastasis. Further experiments suggested that PI3K/AKT, NF-κB, Vimentin, Fibronectin, Snail and Slug were upregulated and E-cadherin was downregulated after calponin 2 was knocked down, implicating altered functions in PDAC proliferation and metastasis. In addition, we verified that calponin 2 functioned through inhibiting PI3K/AKT and NF-κB pathways. Our study suggests that the upregulation of calponin 2 in PDAC correlates to lower malignancy and presents a novel target for the development of new treatment.
钙调蛋白2在调节肌动蛋白细胞骨架方面发挥着重要作用,而肌动蛋白细胞骨架对细胞分裂和迁移至关重要。先前的研究表明,钙调蛋白2可抑制前列腺癌细胞的增殖和转移。然而,钙调蛋白2在胰腺肿瘤生长、转移及患者生存方面的作用仍不清楚。在此,我们证明钙调蛋白2水平是胰腺导管腺癌(PDAC)患者的一个阳性预后因素。肿瘤中钙调蛋白2表达高的患者发生淋巴结转移的情况较少,生存期更长。敲低钙调蛋白2可促进胰腺癌细胞的增殖和转移。进一步的实验表明,敲低钙调蛋白2后,PI3K/AKT、NF-κB、波形蛋白、纤连蛋白、Snail和Slug上调,而E-钙黏蛋白下调,这意味着PDAC增殖和转移功能发生了改变。此外,我们证实钙调蛋白2通过抑制PI3K/AKT和NF-κB途径发挥作用。我们的研究表明,PDAC中钙调蛋白2的上调与较低的恶性程度相关,并为新治疗方法的开发提供了一个新靶点。