CBX7 suppresses cell proliferation, migration, and invasion through the inhibition of PTEN/Akt signaling in pancreatic cancer

Abstract

// Sujie Ni 1, * , Hongwei Wang 1, 2, * , Xiaolin Zhu 3 , Chunhua Wan 4 , Junfei Xu 5 , Chen Lu 6 , Li Xiao 6 , Jiaqi He 2 , Chongyi Jiang 2 , Wei Wang 2 , Zhixian He 5 1 Department of Medical Oncology, Affiliated Hospital of Nantong University, Nantong University, Nantong 226001, China 2 Bilary and Pancreatic Center, Huadong Hospital of Fudan University, Fudan University, Shanghai 200040, China 3 Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong University, Nantong 226001, China 4 Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong 226001, China 5 Department of General Surgery, Affiliated Hospital of Nantong University, Nantong University, Nantong 226001, China 6 Department of Pathology, Huadong Hospital of Fudan University, Fudan University, Shanghai 200040, China * These authors have contributed equally to this work Correspondence to: Zhixian He, email: hezhixian@ntu.edu.cn Wei Wang, email: hdwangwei@fudan.edu.cn Keywords: CBX7, pancreatic cancer, prognosis, tumor suppression, PTEN Received: April 23, 2016      Accepted: November 21, 2016      Published: December 20, 2016 ABSTRACT 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.