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MDFI promotes the proliferation and tolerance to chemotherapy of colorectal cancer cells by binding ITGB4/LAMB3 to activate the AKT signaling pathway

MDFI promotes the proliferation and tolerance to chemotherapy of colorectal cancer cells by binding ITGB4/LAMB3 to activate the AKT signaling pathway

Authors :
Ma, Ding
Liu, Shuwen
Liu, Kua
Kong, Lingkai
Xiao, Lingjun
Xin, Qilei
Jiang, Chunping
Wu, Junhua
Source :
Cancer Biology and Therapy; December 2024, Vol. 25 Issue: 1
Publication Year :
2024

Abstract

ABSTRACTColorectal cancer (CRC) is one of the most lethal cancers. Single-cell RNA sequencing (scRNA-seq) and protein-protein interactions (PPIs) have enabled the systematic study of CRC. In our research, the activation of the AKT pathway in CRC was analyzed by KEGG using single-cell sequencing data from the GSE144735 dataset. The correlation and PPIs of MDFI and ITGB4/LAMB3 were examined. The results were verified in the TCGA and CCLE and further tested by coimmunoprecipitation experiments. The effect of MDFI on the AKT pathway via ITGB4/LAMB3 was validated by knockdown and lentiviral overexpression experiments. The effect of MDFI on oxaliplatin/fluorouracil sensitivity was probed by colony formation assay and CCK8 assay. We discovered that MDFI was positively associated with ITGB4/LAMB3. In addition, MDFI was negatively associated with oxaliplatin/fluorouracil sensitivity. MDFI upregulated the AKT pathway by directly interacting with LAMB3 and ITGB4 in CRC cells, and enhanced the proliferation of CRC cells via the AKT pathway. Finally, MDFI reduced the sensitivity of CRC cells to oxaliplatin and fluorouracil. In conclusion, MDFI promotes the proliferation and tolerance to chemotherapy of colorectal cancer cells, partially through the activation of the AKT signaling pathway by the binding to ITGB4/LAMB3. Our findings provide a possible molecular target for CRC therapy.

Details

Language :
English
ISSN :
15384047 and 15558576
Volume :
25
Issue :
1
Database :
Supplemental Index
Journal :
Cancer Biology and Therapy
Publication Type :
Periodical
Accession number :
ejs68287116
Full Text :
https://doi.org/10.1080/15384047.2024.2314324