title: Crk-like adapter protein is required for TGF-β-induced AKT and ERK-signaling pathway in epithelial ovarian carcinomas.
abstract: Crk-like adapter protein (CrkL) was identified as an important biomarker in epithelial ovarian carcinomas. At the same time, the transforming growth factor β (TGF-β) pathway plays a key role in oncogenesis of advanced cancers. However, more detailed regulation mechanisms are still unclear. So we investigated the role of CrkL in TGF-β pathways in epithelial ovarian carcinomas. The small interfering RNA (siRNA) was used to suppress CrkL in serous papillary cystic adenocarcinoma (SKOV-3) cell line, TGF-β downstream signal molecules AKT and ERK phosphorylation status was tested using the Western blot. Wound healing assay was used to evaluate the capacity of cell migration and proliferation. In this study, CrkL can be activated by TGF-β1 treatment and inhibited by siCrkL. CrkL knockdown markedly suppressed the phosphorylated ERK (p-ERK) as well as the phosphorylated AKT (p-AKT) (p < 0.001) compared with control or TGF-β1 alone. On the other hand, CrkL knockdown could significantly affect SKOV3 wound closure (p < 0.001) using wound healing assay compared to siControl. In conclusion, CrkL protein is required for TGF-β signal pathways through AKT and ERK pathway, which can mediate the development of epithelial ovarian carcinomas. CrkL plays a key regulation role in TGF-β signaling pathway of epithelial ovarian carcinomas, and this study suggested CrkL could be suggested as an efficient target in ovarian cancer treatment.
authors.affiliation: Department of Gynecology, Affiliated Hospital of Shandong Academy of Medical Sciences, 38# Wuyingshan Road, 250031, Jinan, Shandong, China, chengsmshandong@163.com.
authors.forename: Shaomei
authors.initials: S
authors.lastname: Cheng
authors.forename: Jingyan
authors.initials: J
authors.lastname: Guo
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.forename: Lin
authors.initials: L
authors.lastname: Han
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000096:biosynthesis* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010766:Phosphorylation; D016212:Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C082869:CRKL protein; D009687:Nuclear Proteins; D016212:Transforming Growth Factor beta; D051058:Oncogene Protein v-akt