Upregulation of CDC25B by transcription factor TEAD4 drives invasion and inhibits cisplatin sensitivity through cell adhesion in stomach adenocarcinoma.

Autor:	Zhang T; Department of General Surgery, The Fourth Hospital of Changsha City., Chen L; Department of General Surgery, Hunan Children's Hospital., Li S; Department of Geriatrics, The Second Xiangya Hospital, Central South University., Shen C; Disinfection Supply Room, The Fourth Hospital of Changsha City, Changsha, China.
Jazyk:	angličtina
Zdroj:	Anti-cancer drugs [Anticancer Drugs] 2024 Nov 01; Vol. 35 (10), pp. 922-931. Date of Electronic Publication: 2024 Jul 22.
DOI:	10.1097/CAD.0000000000001645
Abstrakt:	Cisplatin is crucial in management of advanced stomach adenocarcinoma, whereas development of chemotherapy resistance hinders overall efficacy of cisplatin. This work aims to explore role of CDC25B in cisplatin sensitivity in stomach adenocarcinoma and offer a possible mechanism for explaining its function. By using bioinformatics approaches, CDC25B and TEAD4 expression levels in stomach adenocarcinoma tissues and enriched pathways of CDC25B were analyzed. qRT-PCR of CDC25B and TEAD4 expression in stomach adenocarcinoma cells, CCK-8 detection of cell viability and IC 50 values, and colony formation assay on cell proliferation were performed. Cell adhesion experiment detected cell adhesion ability. Western blot detected expression of proteins related to cell adhesion, specifically Muc-1, ICAM-1, VCAM-1. Dual luciferase assay and ChIP experiment verified binding relationship between TEAD4 and CDC25B. CDC25B was upregulated in stomach adenocarcinoma tissues and cells, enriched in focal adhesion pathway. Treatment with cell adhesion inhibitors revealed that CDC25B overexpression inhibits the sensitivity of stomach adenocarcinoma to cisplatin through the cell adhesion pathway. CDC25B has an upstream transcription factor TEAD4, which targeted and bound to CDC25B and was highly expressed in stomach adenocarcinoma. Rescue experiment revealed that knocking down TEAD4 weakened suppressive impact of CDC25B overexpression on sensitivity of stomach adenocarcinoma cells to cisplatin. Transcription factor TEAD4 could activate the transcription of CDC25B through cell adhesion to drive cell invasion and reduce sensitivity of stomach adenocarcinoma to cisplatin. TEAD4 and CDC25B may become new targets for management of stomach adenocarcinoma. (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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