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CBX7 suppresses cell proliferation, migration, and invasion through the inhibition of PTEN/Akt signaling in pancreatic cancer
- Source :
- Oncotarget
- Publication Year :
- 2016
- Publisher :
- Impact Journals, LLC, 2016.
-
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.
- Subjects :
- Male
0301 basic medicine
PTEN
Pathology
Time Factors
pancreatic cancer
medicine.disease_cause
0302 clinical medicine
Cell Movement
Polycomb Repressive Complex 1
biology
Middle Aged
Gene Expression Regulation, Neoplastic
Oncology
030220 oncology & carcinogenesis
Adenocarcinoma
Immunohistochemistry
Female
Fluorouracil
tumor suppression
Carcinoma, Pancreatic Ductal
Signal Transduction
Research Paper
Antimetabolites, Antineoplastic
medicine.medical_specialty
Mice, Nude
Transfection
03 medical and health sciences
Cell Line, Tumor
Pancreatic cancer
Biomarkers, Tumor
medicine
Animals
Humans
Neoplasm Invasiveness
Protein kinase B
PI3K/AKT/mTOR pathway
Cell Proliferation
business.industry
Cell growth
Tumor Suppressor Proteins
PTEN Phosphohydrolase
medicine.disease
Pancreatic Neoplasms
030104 developmental biology
Drug Resistance, Neoplasm
CBX7
Cancer research
biology.protein
prognosis
Neoplasm Grading
Carcinogenesis
business
Proto-Oncogene Proteins c-akt
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....8cc1f3adb35265c59ed1756b329344c6