Tyrosine phosphatase SHP2 accelerated ovarian cancer via modulating integrin/ E-Cadherin/ ZEB1 induced EMT

• Published in: Scientific reports Vol. 15; no. 1; pp. 1535 - 13
• Main Authors: Li, Xiaofei, Zhang, Haibo, Dong, Jianan, Wang, Juan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.01.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67; 631/80; Animals; Antigens, CD - genetics; Antigens, CD - metabolism; Bioinformatics; Butyl benzyl phthalate; Cadherins - genetics; Cadherins - metabolism; Cancer; Cell Line, Tumor; Cell migration; Cell Movement; E-cadherin; Eintegrin/E-Cadherin signalling pathway; Epidermal growth factor; Epithelial mesenchymal transition; Epithelial-Mesenchymal Transition - genetics; Female; Gene Expression Regulation, Neoplastic; Humanities and Social Sciences; Humans; Integrins - metabolism; Invasiveness; Mice; Mice, Nude; Molecular modelling; multidisciplinary; Ovarian cancer; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Phosphatase; Protein Tyrosine Phosphatase, Non-Receptor Type 11 - genetics; Protein Tyrosine Phosphatase, Non-Receptor Type 11 - metabolism; Protein-tyrosine-phosphatase; Science; Science (multidisciplinary); SHP2; Smad2 protein; Tumors; Western blotting; Zinc Finger E-box-Binding Homeobox 1 - genetics; Zinc Finger E-box-Binding Homeobox 1 - metabolism; SHP2; Epithelial mesenchymal transition; Eintegrin/E-Cadherin signalling pathway; Ovarian cancer
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-025-85445-w

This article focusing on examining the function and further, molecular function of SHP2 in ovarian cancer (OC). For the molecular mechanism, bioinformatics was applied to study the specifically expressed genes in ovarian cancer ; the western blotting was applied to identify the EGF, p-SHP2, ZEB1, and E-Cadherin expressions in ovarian cancer tissue and pair adjacent tissue; then SKOV3 cells were treated with EGF and infected with E-Cadherin overexpression lentivirus, and then cells were treated with benzyl butyl phthalate and IRS-1 respectively. Detection of expression of p-SHP2, ZEB1, E-Cadherin, α3-integrin, p-Src, p-SMAD2, Snail, Slug and SKOV3 cells of migration and invasion abilities were detected using Western blot method and cell scratch assay and Transwell assay; Progression of ovarian cancer was detected using subcutaneous tumor transplantation assay in nude mice and HE staining method and immunocyto. The bioinformatics analysis results suggested that SHP2 is highly specifically expressed and E-Cadherin, which is low specifically expressed in ovarian cancer tissues, while EGF, p-SHP2 or ZEB1 are highly expressed and E-Cadherin is low expressed in ovarian cancer tissues; Overexpression of E-Cadherin could reduce the expressions of p-SHP2, ZEB1, α3-integrin, p-Src, p-SMAD2, Snail and Slug might has roles in alleviating the ovarian cancer development and decreasing the levels of p-SHP2 and ZEB1 in tumor samples. And E-Cadherin overexpression reduced the migration and invasion ability of SKOV3 cells. SHP2 tyrosine phosphatase enhances the ovarian cancer cells’ motility and invasiveness by upregulation of the integrin/E-Cadherin switch through ZEB1 signal.