Phosphorylation of small kinetochore-associated protein induced by GSK3β promotes cell migration and invasion in esophageal cancer. Issue 9 (3rd May 2022)

• Record Type: Journal Article
• Authors: Qin, Bo; Zhu, Zhu; Yin, Fanxiang; Yan, Dan; Wan, Jiajia; Dong, Meng; Wang, Zhengyang
• Is Part Of: Cell cycle. Volume 21:Issue 9(2022)
• Page Start: 972
• Page End: 983
• Publication Date: 2022-05-03
• Subjects: Esophageal cancer -- GSK-3β -- SKAP -- phosphorylation; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2022.2038847
• Languages: English
• ISSNs: 1538-4101

Abstract

ABSTRACT: Glycogen synthesis kinase-3β (GSK-3β) is a kinase shown to regulate esophageal cancer (EC) progression. However, the significance of GSK-3β in phosphorylation of small kinetochore-associated protein (SKAP) has not been fully characterized. GSK-3β/SKAP expression was analyzed in EC tissues by RT-qPCR. The association between GSK-3β expression and the overall survival was analyzed using the Kaplan–Meier method. Transwell and wound healing assays were performed to assess the effects of GSK-3β/SKAP knockdown on EC cell migration and invasion. By in vitro kinase assay, the SKAP T294 site was identified as a phosphorylated target of GSK-3β. Moreover, we established two cell lines expressing either T294D (phosphor-mimic) or T294A (phosphor-deficiency) SKAP to analyze the effect of SKAP phosphorylation on EC cell invasion, migration, and epithelial–mesenchymal transition (EMT) process. GSK-3β was overexpressed and positively correlated with SKAP levels in EC tissues. Increased GSK-3β expression was associated with EC poor prognosis. Both of GSK-3β knockdown and silencing SKAP decreased EC cell migration and invasion. GSK-3β phosphorylated SKAP protein at Thr294 site. Additionally, a T294D mutant SKAP enhanced cell migration, invasion, and EMT process. Conversely, a T294A mutant SKAP inhibited EC cell malignancy. Meanwhile, cell invasion and migration abilities were inhibited after silencing GSK-3β in EC109-WT, EC109-T294A and EC109-T294D cells. Phosphorylation of SKAP induced by GSK-3β promoted EC cell migration and invasion.