Glycogen Synthase Kinase-3 Beta (GSK3β)-mediated Phosphorylation of ETS1 Promotes Progression of Ovarian Carcinoma

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2021 May 23

PMID 34023818

Citations 1

Authors

Chia-Lung Tsai

Shih-Ming Jung

Lang-Ming Chi

Chi-Neu Tsai

Chiao-Yun Lin

Angel Chao

Yun-Shien Lee

Affiliations

Soon will be listed here.

Abstract

ETS1 - an evolutionarily conserved transcription factor involved in the regulation of a number of cellular processes - is overexpressed in several malignancies, including ovarian cancer. Most studies on ETS1 expression have been focused on the transcriptional and RNA levels, with post-translational control mechanisms remaining relatively unexplored in the pathogenesis of malignancies. Here, we show that ETS1 forms a complex with glycogen synthase kinase-3β (GSK3β). Specifically, GSK3β-mediated phosphorylation of ETS1 at threonine 265 and serine 269 promoted protein stability, induced the transcriptional activation of matrix metalloproteinase (), and increased cell migration. experiments revealed that a GSK3β inhibitor was able to suppress both endogenous ETS1 expression and induction of expression. Upon generation of a specific antibody against phosphorylated ETS1, we demonstrated that phospho-ETS1 immunohistochemical expression in ovarian cancer specimens was correlated with that of MMP-9. Notably, the cumulative overall survival of patients with low phospho-ETS1 histoscores was significantly longer than that of those showing higher scores. We conclude that the GSK3β/ETS1/MMP-9 axis may regulate the biological aggressiveness of ovarian cancer and can serve as a prognostic factor in patients with this malignancy.

Citing Articles

Comprehensive analysis of ETS1 expression and its prognostic value in clear cell renal cell carcinoma.

Mo M, Zhu Q, Yang L, Deng Y, Yu Y, Zhou Z Am J Transl Res. 2024; 16(4):1062-1080.

PMID: 38715839 PMC: 11070354. DOI: 10.62347/QNSV5278.

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