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m6A‐Dependent Modulation via IGF2BP3/MCM5/Notch Axis Promotes Partial EMT and LUAD Metastasis.
- Source :
- Advanced Science; 7/18/2023, Vol. 10 Issue 20, p1-15, 15p
- Publication Year :
- 2023
-
Abstract
- The importance of mRNA N6‐methyladenosine (m6A) modification during tumor metastasis is controversial as it plays distinct roles in different biological contexts. Moreover, how cancer cell plasticity is shaped by m6A modification is interesting but remains uncharacterized. Here, this work shows that m6A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) is remarkably upregulated in metastatic lung adenocarcinoma (LUAD) and indicates worse prognosis of patients. Interestingly, IGF2BP3 induces partial epithelial‐mesenchymal‐transition (EMT) and confers LUAD cells plasticity to metastasize through m6A‐dependent overactivation of Notch signaling. Mechanistically, IGF2BP3 recognized m6A‐modified minichromosome maintenance complex component (MCM5) mRNAs to prolong stability of them, subsequently upregulating MCM5 protein, which competitively inhibits SIRT1‐mediated deacetylation of Notch1 intracellular domain (NICD1), stabilizes NICD1 protein and contributes to m6A‐dependent IGF2BP3‐mediated cellular plasticity. Notably, a tight correlation of the IGF2BP3/MCM5/Notch axis is evidenced in clinical LUAD specimens. Therefore, this study elucidates a critical role of m6A modification on LUAD cell plasticity in fostering tumor metastasis via the above axis, providing potential targets for metastatic LUAD. [ABSTRACT FROM AUTHOR]
- Subjects :
- CARRIER proteins
NOTCH genes
METASTASIS
ADENOSINES
PROTHROMBIN
CANCER cells
SIRTUINS
Subjects
Details
- Language :
- English
- ISSN :
- 21983844
- Volume :
- 10
- Issue :
- 20
- Database :
- Complementary Index
- Journal :
- Advanced Science
- Publication Type :
- Academic Journal
- Accession number :
- 167301473
- Full Text :
- https://doi.org/10.1002/advs.202206744