title: CCN1 promotes tumorigenicity through Rac1/Akt/NF-κB signaling pathway in pancreatic cancer.
abstract: 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.
authors: Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, People's Republic of China.
authors: Xuqing
authors: X
authors: Wang
authors: Yuezhen
authors: Y
authors: Deng
authors: Zhengfa
authors: Z
authors: Mao
authors: Xiaoyan
authors: X
authors: Ma
authors: Xin
authors: X
authors: Fan
authors: Lei
authors: L
authors: Cui
authors: Jianguo
authors: J
authors: Qu
authors: Dong
authors: D
authors: Xie
authors: Jianxin
authors: J
authors: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D055515:Cysteine-Rich Protein 61 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D047368:Tumor Burden; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D055515:Cysteine-Rich Protein 61; D016328:NF-kappa B; D051057:Proto-Oncogene Proteins c-akt; D020830:rac1 GTP-Binding Protein