CCN1 promotes tumorigenicity through Rac1/Akt/NF-κB signaling pathway in pancreatic cancer
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Aberrant CCN1 expression has been reported to play an important role in the tumor development. However, the pattern and the role of CCN1 in pancreatic cancer remain largely unknown. Therefore, we further deciphered the role CCN1 played in pancreatic cancer. We first evaluated the CCN1 expression in human pancreatic cancer tissues and pancreatic cancer cells. Then we forced expression and silenced CCN1 expression in pancreatic cancer cell lines MIA PaCa2 and PANC-1 respectively, using lentivirus vectors. We characterized the stable cells in vitro and in vivo using a nude mouse xenograft model. In this study, we found that CCN1 expression was significantly higher in cancer specimens which positively correlated with the expression level of phosphorylated Akt and p65. and poorer outcome. Moreover, our results demonstrated that CCN1 positively regulated pancreatic cell growth in vitro and in vivo and helped cancer cells resist to tumor necrosis factor alpha-induced apoptosis. Furthermore, we disclosed that activation of CCN1/ras-related c3 botulinum toxin substrate 1 (Rac1)/V-akt murine thymoma viral oncogene homolog (Akt)/nuclear factor-kappa B pathway inhibited apoptosis in pancreatic cancer cells. CCN1 is upregulated in pancreatic cancer and promotes the survival of pancreatic cancer cells. Taken together, these results indicate that CCN1 may be a potential target for pancreatic cancer therapy.
KeywordsCCN1 Pancreatic ductal adenocarcinoma Apoptosis NF-κB pathway
This work was sponsored by the National Natural Science Foundation of China, grant number 81070287 and Zhenjiang Science and Technology Pillar Program, grant numbers SH2009013 and SH2011026.
Conflicts of interest
- 7.Grzeszkiewicz TM, Lindner V, Chen N, Lam SC, Lau LF. The angiogenic factor cysteine-rich 61 (cyr61, ccn1) supports vascular smooth muscle cell adhesion and stimulates chemotaxis through integrin alpha(6)beta(1) and cell surface heparan sulfate proteoglycans. Endocrinology. 2002;143:1441–50.PubMedGoogle Scholar
- 27.Wang Z, Li Y, Banerjee S, Kong D, Ahmad A, Nogueira V, et al. Down-regulation of Notch-1 and Jagged-1 inhibits prostate cancer cell growth, migration and invasion, and induces apoptosis via inactivation of Akt, mTOR, and NF-kappaB signaling pathways. J Cell Biochem. 2010;109:726–36.PubMedGoogle Scholar
- 41.Chaturvedi P, Singh AP, Moniaux N, Senapati S, Chakraborty S, Meza JL, et al. Muc4 mucin potentiates pancreatic tumor cell proliferation, survival, and invasive properties and interferes with its interaction to extracellular matrix proteins. Mol Cancer Res. 2007;5:309–20.CrossRefPubMedGoogle Scholar