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Published VersionCC BY V4.0, Open Access
Journal article
A stop-gain mutation in GXYLT1 promotes metastasis of colorectal cancer via the MAPK pathway
Cell Death & Disease, Vol.13(4), pp.1-12
2022
Appears in Cancer Research Cluster Research Collection
Abstract
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 HospitalMin Zhao (Author) - University of the Sunshine Coast, Queensland, GeneCology Research Centre - LegacyTianqi Liu (Author) - Peking University Cancer HospitalJiangbo Chen (Author) - Peking University Cancer HospitalPin Gao (Author) - Peking University Cancer HospitalLei Chen (Author) - Peking University Cancer HospitalPu Xing (Author) - Peking University Cancer HospitalZaozao Wang (Author) - Peking University Cancer HospitalJiabo Di (Author) - Peking University Cancer HospitalQiang Xu (Author) - GenomiCare Biotechnology (Shanghai, China)Hong Qu (Corresponding Author) - Peking UniversityBeihai Jiang (Corresponding Author) - Peking University Cancer HospitalXiangqian 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; 2041-4889
- 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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