title: Epidermal growth factor receptor kinase substrate 8 promotes the metastasis of cervical cancer via the epithelial-mesenchymal transition.
abstract: Epidermal growth factor receptor pathway substrate 8 (Eps8) has been identified as a novel substrate for epidermal growth factor receptor (EGFR) kinase and is involved in EGFR‑mediated signaling pathways correlated with tumorigenesis, proliferation and metastasis in various cancer types. However, the precise role of Eps8 in cervical cancer metastasis remains to be elucidated. Immunohistochemistry revealed that Eps8 was significantly increased in cervical cancer specimens compared with squamous intraepithelial lesion and normal cervical tissues. Additionally, it was revealed that Eps8 expression not only correlated with cervical cancer progression, but also exhibited a close correlation with the epithelial‑mesenchymal transition (EMT) markers, E‑cadherin and vimentin. Furthermore, the present study focused predominantly on the EMT‑associated role of Eps8 in the EMT, migration and invasion of cervical cancer cells. Eps8‑short hairpin (sh)RNA was transfected into HeLa and SiHa cells to deplete its expression, and reverse transcription-quantitative polymerase chain reaction and western blot analyses were performed to confirm Eps8‑knockdown and to investigate the influence of Eps8 on EMT markers. The present findings have revealed that Eps8 silencing led to the upregulation of the epithelial marker E‑cadherin, while expression of the mesenchymal marker vimentin and the transcription factor snail was decreased at both mRNA and protein expression levels. Transwell cell migration and Matrigel invasion assays showed that downregulation of Eps8 significantly inhibited cell migration and invasion of HeLa and SiHa cells. Taken together, these results suggested that Eps8 promotes cervical cancer metastasis by orchestrating the EMT.
authors: Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital of China Welfare Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China.
authors: Qian
authors: Q
authors: Li
authors: Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital of China Welfare Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China.
authors: Wei
authors: W
authors: Bao
authors: Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital of China Welfare Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China.
authors: Qiong
authors: Q
authors: Fan
authors: Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital of China Welfare Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China.
authors: Wen-Jing
authors: WJ
authors: Shi
authors: Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital of China Welfare Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China.
authors: Zhu-Nan
authors: ZN
authors: Li
authors: Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital of China Welfare Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China.
authors: Ying
authors: Y
authors: Xu
authors: Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital of China Welfare Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China.
authors: Dan
authors: D
authors: Wu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000235:genetics*; D000328:Adult; D000368:Aged; D015820:Cadherins / Q000032:analysis / Q000235:genetics; D002465:Cell Movement; D002584:Cervix Uteri / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology; D014746:Vimentin / Q000032:analysis / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; C489989:EPS8 protein, human; D034741:RNA, Small Interfering; D014746:Vimentin