Downregulation of VMP1 confers aggressive properties to colorectal cancer.
Vacuole membrane protein 1 (VMP1) was recently found to be involved in the process of tumor metastasis and is also considered to play a vital role in balancing apoptosis and autophagy. In the present study, the expression of VMP1 in colorectal cancer and matched adjacent non‑cancerous tissues was evaluated by immunohistochemistry (IHC) for studying the role of VMP1 in the process of colorectal cancer. Kaplan‑Meier analysis and the log-rank test were used to calculate the correlation of classic clinicopathological characteristics related to survival and the expression of VMP1. In vitro, a VMP1 stable gene silencing cell model was constructed using a lentiviral vector. The invasive ability and proliferation of colorectal cancer cells were evaluated by Transwell and MTT assays, respectively, and the underlying signaling pathway was explored by western blotting. Additionally, drug susceptibility to cisplatin, oxaliplatin and 5-FU was tested before and after VMP1 knockout. Finally, an animal model was constructed to explore the role of VMP1 in the physiopathologic process of colorectal cancer. Our results indicated that VMP1 showed increased expression in the adjacent non-cancer tissues compared with that in the colorectal cancer tissues. For different stages of colorectal cancer, expression of VMP1 had a negative correlation with the malignancy of the cancer. In clinical research, we also found that the median survival of patients with low VMP1 expression was much shorter than the survival of patients with high expression. In vitro, after infection with the lentivirus, cells with VMP1 knockout gained significant aggressive properties in regards to invasion and proliferation, and the mechanisms may be related to the activation of the PI3K/Akt/ZO-1/E-cadherin pathway. We also found that shVMP1 cells were more sensitive to 5-FU, but not cisplatin and oxaliplatin. Finally, we found a higher number of formed nodules in nude mice after intraperitoneal injection with shVMP1 cells in the in vivo study.
Department of Medical Oncology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Pudong, Shanghai 201399, P.R. China.
Xian-Zhi
XZ
Guo
Drugs and Pharmacology Laboratory, Ningbo Institute of Medical Sciences, Ningbo, Zhejiang 315020, P.R. China.
Xiao-Lei
XL
Ye
Department of Internal Neurology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Pudong, Shanghai 201399, P.R. China.
Wei-Zhong
WZ
Xiao
Department of Pharmacology, China Pharmaceutical University, Nanjing, Jiangsu 211198, P.R. China.
Xue-Ni
XN
Wei
Department of Pathology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Pudong, Shanghai 201399, P.R. China.
Qing-Hua
QH
You
Drugs and Pharmacology Laboratory, Ningbo Institute of Medical Sciences, Ningbo, Zhejiang 315020, P.R. China.
Xiao-Hang
XH
Che
Department of Internal Neurology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Pudong, Shanghai 201399, P.R. China.
Yan-Jun
YJ
Cai
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P.R. China.
Fang
F
Chen
Department of General Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Pudong, Shanghai 201399, P.R. China.
Hao
H
Yuan
Department of Medical Oncology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Pudong, Shanghai 201399, P.R. China.
Xiao-Jian
XJ
Liu
Department of Medical Oncology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Pudong, Shanghai 201399, P.R. China.
Ming-Hua
MH
Yu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000494:pharmacology; D000077150:Oxaliplatin; D011379:Prognosis; D016019:Survival Analysis
D008565:Membrane Proteins; D009944:Organoplatinum Compounds; C526584:VMP1 protein, human; D000077150:Oxaliplatin; D005472:Fluorouracil