Ni Sujie, Wang Hongwei, Zhu Xiaolin, Wan Chunhua, Xu Junfei, Lu Chen, Xiao Li, He Jiaqi, Jiang Chongyi, Wang Wei, He Zhixian
Department of Medical Oncology, Affiliated Hospital of Nantong University, Nantong University, Nantong 226001, China.
Bilary and Pancreatic Center, Huadong Hospital of Fudan University, Fudan University, Shanghai 200040, China.
Oncotarget. 2017 Jan 31;8(5):8010-8021. doi: 10.18632/oncotarget.14037.
Chromobox protein homolog 7 (CBX7), one of the polycomb group (PcG) proteins, is a transcriptional repressor involved in the regulation of cell proliferation and senescence. In the present study, we showed that CBX7 negatively regulates the proliferation, viability, chemoresistance, and migration of pancreatic cancer cells. Overexpression of CBX7 significantly inhibited the proliferation of pancreatic cancer cells in vitro and in vivo. Depletion of CBX7 facilitated their growth. CBX7 also impaired the viability and chemoresistance of pancreatic cancer cells. Transwell assays showed that CBX7 reduces the migratory capacity of pancreatic cancer cells. Of note, CBX7 reduced PTEN/Akt signaling in pancreatic cancer cells by increasing PTEN transcription, suggesting involvement of PTEN/Akt pathway in the tumor suppressive activity of CBX7. In addition, immunohistochemical analysis the CBX7 and PTEN expression in 74 surgically resected pancreatic ductal adenocarcinoma (PDAC) specimens revealed that CBX7 expression is significantly downregulated in pancreatic ductal adenocarcinoma, compared to normal pancreatic tissues. Reduced expression of CBX7 and PTEN was associated with increased malignancy grade in pancreatic adenocarcinoma, whereas maintenance of CBX7 and PTEN expression showed a trend toward a longer survival. These findings suggest CBX7 is an important tumor suppressor that negatively modulates PTEN/Akt signaling during pancreatic tumorigenesis.
染色体盒蛋白同源物7（CBX7）是多梳蛋白家族（PcG）的成员之一，是一种参与细胞增殖和衰老调控的转录抑制因子。在本研究中，我们发现CBX7对胰腺癌细胞的增殖、活力、化疗耐药性和迁移具有负向调节作用。CBX7的过表达在体外和体内均显著抑制胰腺癌细胞的增殖。CBX7的缺失则促进其生长。CBX7还损害胰腺癌细胞的活力和化疗耐药性。Transwell实验表明，CBX7降低了胰腺癌细胞的迁移能力。值得注意的是，CBX7通过增加PTEN转录来降低胰腺癌细胞中的PTEN/Akt信号传导，提示PTEN/Akt通路参与了CBX7的肿瘤抑制活性。此外，对74例手术切除的胰腺导管腺癌（PDAC）标本进行CBX7和PTEN表达的免疫组化分析显示，与正常胰腺组织相比，胰腺导管腺癌中CBX7的表达显著下调。CBX7和PTEN表达的降低与胰腺腺癌恶性程度的增加相关，而CBX7和PTEN表达的维持则显示出患者生存期延长的趋势。这些发现表明，CBX7是一种重要的肿瘤抑制因子，在胰腺肿瘤发生过程中对PTEN/Akt信号传导起负向调节作用。
