CEMIP, a Novel Adaptor Protein of OGT, Promotes Colorectal Cancer Metastasis Through Glutamine Metabolic Reprogramming Via Reciprocal Regulation of β-catenin

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2021 Oct 5

PMID 34608265

Citations 25

Authors

Qingling Hua

Biying Zhang

Guojie Xu

Lanqing Wang

Haihong Wang

Zhenyu Lin

Dandan Yu

Jinghua Ren

Dejun Zhang

Lei Zhao

Tao Zhang

Affiliations

Soon will be listed here.

Abstract

Metastasis is the leading cause of colorectal cancer (CRC)-induced death. However, the underlying molecular mechanisms of CRC metastasis are poorly understood. Metabolic reprogramming is an intrinsic feature of cancer, which have complicated effects on cancer metastasis. Here, we find that a novel metastasis-related protein, cell migration-inducing and hyaluronan-binding protein (CEMIP), can act as a novel adaptor protein of O-GlcNAc transferase (OGT) to promote CRC metastasis through glutamine metabolic reprogramming. Mechanistically, CEMIP interacts with OGT and β-catenin, which leads to elevated O-GlcNAcylation of β-catenin and enhanced β-catenin nuclear translocation from cytomembrane. Furthermore, accumulated β-catenin in nucleus enhances the transcription of CEMIP to reciprocally regulate β-catenin and contributes to over-expression of glutaminase 1 and glutamine transporters (SLC1A5 and SLC38A2). Combinational inhibition of CEMIP and glutamine metabolism could dramatically attenuate the metastasis of CRC in vivo. Collectively, this study reveals the importance of glutamine metabolic reprogramming in CEMIP-induced CRC metastasis, indicating the great potential of CEMIP and glutamine metabolism for CRC metastasis prevention.

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