MAPK/ERK signaling pathway-induced hyper-O-GlcNAcylation enhances cancer malignancy

Molecular and Cellular Biochemistry
Xinling ZhangYuchao Gu

Abstract

Dysregulated MAPK/ERK signaling is implicated in one-third of human tumors and represents an attractive target for the development of anticancer drugs. Similarly, elevated protein O-GlcNAcylation and O-GlcNAc transferase (OGT) are detected in various cancers and serve as attractive novel cancer-specific therapeutic targets. However, the potential connection between them remains unexplored. Here, a positive correlation was found between the activated MAPK/ERK signaling and hyper-O-GlcNAcylation in various cancer types and inhibition of the MAPK/ERK signaling by 10 µM U0126 significantly decreased the expression of OGT and O-GlcNAcylation in H1299, BPH-1 and DU145 cells; then, the pathway analysis of the potential regulators of OGT obtained from the UCSC Genome Browser was done, and ten downstream targets of ERK pathway were uncovered; the following results showed that ELK1, one of the ten targets of ERK pathway, mediated ERK signaling-induced OGT upregulation; finally, the MTT assay and the soft agar assay showed that the inhibition of MAPK/ERK signaling reduced the promotion effect of hyper-O-GlcNAcylation on cancer cell proliferation and anchorage-independent growth. Taken together, our data originally provided evidence for th...Continue Reading

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Citations

Jul 20, 2016·Oncology Reports·Ming WanYun-Fu Cui
Mar 16, 2017·Preparative Biochemistry & Biotechnology·Jieqiong QiYuchao Gu
Feb 27, 2017·Cellular and Molecular Neurobiology·Rongrong ChenXiaojuan Liu
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Nov 4, 2020·Biomolecules·Jie L Tian, Farzad Islami Gomeshtapeh
Mar 2, 2021·World Journal of Gastrointestinal Surgery·Yao Liu, Fang-Xing Peng
Jun 28, 2016·Journal of Molecular Biology·Christina M FerrerMauricio J Reginato
Aug 22, 2021·Endocrinology·Logan J MassmanStephanie Olivier-Van Stichelen
Jun 6, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Wei Kang Cheng, Chern Ein Oon

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