Research Papers:
CBX7 suppresses cell proliferation, migration, and invasion through the inhibition of PTEN/Akt signaling in pancreatic cancer
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Abstract
Sujie Ni1,*, Hongwei Wang1,2,*, Xiaolin Zhu3, Chunhua Wan4, Junfei Xu5, Chen Lu6, Li Xiao6, Jiaqi He2, Chongyi Jiang2, Wei Wang2, Zhixian He5
1Department of Medical Oncology, Affiliated Hospital of Nantong University, Nantong University, Nantong 226001, China
2Bilary and Pancreatic Center, Huadong Hospital of Fudan University, Fudan University, Shanghai 200040, China
3Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong University, Nantong 226001, China
4Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong 226001, China
5Department of General Surgery, Affiliated Hospital of Nantong University, Nantong University, Nantong 226001, China
6Department 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.
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