A stop-gain mutation in GXYLT1 promotes metastasis of colorectal cancer via the MAPK pathway

Lin Peng; Min Zhao; Tianqi Liu; Jiangbo Chen; Pin Gao; Lei Chen; Pu Xing; Zaozao Wang; Jiabo Di; Qiang Xu; Hong Qu; Beihai Jiang; Xiangqian Su

doi:10.1038/s41419-022-04844-3

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A stop-gain mutation in GXYLT1 promotes metastasis of colorectal cancer via the MAPK pathway

Journal article

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A stop-gain mutation in GXYLT1 promotes metastasis of colorectal cancer via the MAPK pathway

Lin Peng, Min Zhao, Tianqi Liu, Jiangbo Chen, Pin Gao, Lei Chen, Pu Xing, Zaozao Wang, Jiabo Di, Qiang Xu, …

Cell Death & Disease, Vol.13(4), pp.1-12

2022

DOI: https://doi.org/10.1038/s41419-022-04844-3

PMCID: PMC9033806

PMID: 35459861

Appears in Cancer Research Cluster Research Collection

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Abstract

cancer genomics

cell signalling

colorectal cancer

metastatis

oncogenes

Genomic instability plays a key role in the initiation and progression of colorectal cancer (CRC). Although cancer driver genes in CRC have been well characterized, identifying novel genes associated with carcinogenesis and treatment remains challenging because of tumor heterogeneity. Here, we analyzed the genomic alterations of 45 samples from CRC patients in northern China by whole-exome sequencing. In addition to the identification of six well-known CRC driver genes (APC, TP53, KRAS, FBXW7, PIK3CA, and PABPC), two tumor-related genes (MTCH2 and HSPA6) were detected, along with RRP7A and GXYLT1, which have not been previously linked to cancer. GXYLT1 was mutated in 40% (18/45) of the samples in our cohort. Functionally, GXYLT1 promoted migration and invasion in vitro and metastasis in vivo, while the GXYLT1S212* mutant induced significantly greater effect. Furthermore, both GXYLT1 and GXYLT1S212* interacted with ERK2. GXYLT1 induced metastasis via a mechanism involving the Notch and MAPK pathways, whereas the GXYLT1S212* mutant mainly promoted metastasis by activating the MAPK pathway. We propose that GXYLT1 acts as a novel metastasis-associated driver gene and GXYLT1S212* might serve as a potential indicator for therapies targeting the MAPK pathway in CRC.

Details

Title: A stop-gain mutation in GXYLT1 promotes metastasis of colorectal cancer via the MAPK pathway
Authors: Lin Peng (Author) - Peking University Cancer Hospital
Min Zhao (Author) - University of the Sunshine Coast, Queensland, GeneCology Research Centre - Legacy
Tianqi Liu (Author) - Peking University Cancer Hospital
Jiangbo Chen (Author) - Peking University Cancer Hospital
Pin Gao (Author) - Peking University Cancer Hospital
Lei Chen (Author) - Peking University Cancer Hospital
Pu Xing (Author) - Peking University Cancer Hospital
Zaozao Wang (Author) - Peking University Cancer Hospital
Jiabo Di (Author) - Peking University Cancer Hospital
Qiang Xu (Author) - GenomiCare Biotechnology (Shanghai, China)
Hong Qu (Corresponding Author) - Peking University
Beihai Jiang (Corresponding Author) - Peking University Cancer Hospital
Xiangqian Su (Corresponding Author) - Peking University Cancer Hospital
Publication details: Cell Death & Disease, Vol.13(4), pp.1-12
Publisher: Nature Publishing Group
Date published: 2022
DOI: 10.1038/s41419-022-04844-3
ISSN: 1476-5403
PMID: 35459861; PMC9033806
Copyright note: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Organisation Unit: University of the Sunshine Coast, Queensland; Cancer Research Cluster; School of Science, Technology and Engineering; Centre for Bioinnovation
Language: English
Record Identifier: 99629434502621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Cell Biology

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