IGF2BP3 promotes the progression of colorectal cancer and mediates cetuximab resistance by stabilizing EGFR mRNA in an m6A-dependent manner

Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an RNA-binding protein, is associated with tumorigenesis and progression. However, the exact molecular mechanisms of IGF2BP3 in colorectal cancer (CRC) oncogenesis, progression, and drug resistance remain unclear. This study found that I...

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Published in:Cell death & disease 2023-09, Vol.14 (9), p.581-581, Article 581
Main Authors: Chen, Li-Jie, Liu, Hui-Ye, Xiao, Zhi-Yuan, Qiu, Ting, Zhang, Dan, Zhang, Ling-Jie, Han, Fang-Yi, Chen, Guo-Jun, Xu, Xue-Mei, Zhu, Jiong-Hua, Ding, Yan-Qing, Wang, Shu-Yang, Ye, Ya-Ping, Jiao, Hong-Li
Format: Article
Language:English
Subjects:
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Antibodies
Biochemistry
Biomarkers
Biomedical and Life Sciences
Cell Biology
Cell Culture
Colorectal cancer
Colorectal carcinoma
Drug resistance
Epidermal growth factor
Epidermal growth factor receptors
Gene expression
Genomics
Immunology
Insulin-like growth factors
Kinases
Life Sciences
Lymphatic system
Medical prognosis
Metastasis
Molecular modelling
mRNA stability
N6-methyladenosine
Pathology
Proteins
RNA-binding protein
Therapeutic targets
Tumorigenesis
Tumors
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Summary:Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an RNA-binding protein, is associated with tumorigenesis and progression. However, the exact molecular mechanisms of IGF2BP3 in colorectal cancer (CRC) oncogenesis, progression, and drug resistance remain unclear. This study found that IGF2BP3 was upregulated in CRC tissues. Clinically, the elevated IGF2BP3 level is predictive of a poor prognosis. Functionally, IGF2BP3 enhances CRC tumorigenesis and progression both in vitro and in vivo. Mechanistically, IGF2BP3 promotes epidermal growth factor receptor (EGFR) mRNA stability and translation and further activates the EGFR pathway by serving as a reader in an N6-methyladenosine (m 6 A)-dependent manner by cooperating with METTL14. Furthermore, IGF2BP3 increases the drug resistance of CRC cells to the EGFR-targeted antibody cetuximab. Taken together, our results demonstrated that IGF2BP3 was a functional and clinical oncogene of CRC. Targeting IGF2BP3 and m 6 A modification may therefore offer rational therapeutic targets for patients with CRC.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-023-06099-y