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

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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.", "claims": [{"id": "claim-method", "statement": "Differences between the two groups were compared by using an independent t-test, and a statistically significant difference was defined as *, p < .05; **, p < .01; ***, and p < .001.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38375821", "locator": "sections[29] \"Statistical analysis\" paragraph 2", "quote": "Differences between the two groups were compared by using an independent t-test, and a statistically significant difference was defined as *, p < .05; **, p < .01; ***, and p < .001."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data underlying this article will be shared on reasonable request to the corresponding author, Junhua Wu (wujunhua@nju.edu.cn).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38375821", "locator": "sections[34] \"Data availability statement\" paragraph 2", "quote": "The data underlying this article will be shared on reasonable request to the corresponding author, Junhua Wu (wujunhua@nju.edu.cn)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "MDFI promotes colorectal cancer cell proliferation and reduces sensitivity to oxaliplatin and fluorouracil, partly through binding to ITGB4/LAMB3 and activating AKT signaling.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38375821", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "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."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "MDFI promotes colorectal cancer cell proliferation and reduces sensitivity to oxaliplatin and fluorouracil, partly through binding to ITGB4/LAMB3 and activating AKT signaling.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:38375821"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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