title: The adaptor protein CrkII regulates IGF-1-induced biological behaviors of pancreatic ductal adenocarcinoma.
abstract: Recently, the adaptor protein CrkII has been proved to function in initiating signals for proliferation and invasion in some malignancies. However, the specific mechanisms underlying insulin-like growth factor 1 (IGF-1)-CrkII signaling-induced proliferation of pancreatic ductal adenocarcinoma (PDAC) were not unraveled. In this work, PDAC tissues and cell lines were subjected to in vitro and in vivo assays. Our findings showed that CrkII was abundantly expressed in PDAC tissues and closely correlated with tumor-node-metastasis (TNM) stage and invasion. When cells were subjected to si-CrkII, si-CrkII inhibited IGF-1-mediated PDAC cell growth. In vitro, we demonstrated the upregulation of CrkII, p-Erk1/2, and p-Akt occurring in IGF-1-treated PDAC cells. Conversely, si-CrkII affected upregulation of CrkII, p-Erk1/2, and p-Akt. In addition, cell cycle and in vivo assay identified that knockdown of CrkII inhibited the entry of G1 into S phase and the increase of PDAC tumor weight. In conclusion, CrkII mediates IGF-1 signaling and further balanced PDAC biological behaviors via Erk1/2 and Akt pathway, which indicates that CrkII gene and protein may act as an effective target for the treatment of PDAC.
authors.affiliation: Department of Endocrinology, China-Japan Union Hospital of Jilin University, Changchun, 130033, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, China-Japan Union Hospital of Jilin University, Changchun, 130033, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Changchun Emergency Center, Changchun, 130021, China.
authors.forename: Guangying
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Endocrinology, People's Hospital of Jilin Province, Changchun, 130021, China.
authors.forename: Kexin
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Endocrinology, China-Japan Union Hospital of Jilin University, Changchun, 130033, China.
authors.forename: Lingli
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, First Hospital of Jilin University, Changchun, 130021, China. xubf@jlu.edu.cn.
authors.forename: Baofeng
authors.initials: B
authors.lastname: Xu
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D011379:Prognosis; D050737:Proto-Oncogene Proteins c-crk / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C583557:IGF1 protein, human; D050737:Proto-Oncogene Proteins c-crk; D034741:RNA, Small Interfering; D007334:Insulin-Like Growth Factor I
keywords: Apoptosis; CrkII; IGF-1; PDAC; Proliferation