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

Sep 22, 2026

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Colorectal cancer (CRC) is among the most lethal malignancies. Using single-cell RNA sequencing and protein-protein interaction analyses, AKT pathway activation in CRC was examined with KEGG and corroborated through TCGA and CCLE verification. MDFI was assessed for its relationship with ITGB4/LAMB3 and for functional impact on tumor growth. Knockdown and lentiviral overexpression confirmed that MDFI enhances CRC proliferation through ITGB4/LAMB3-mediated AKT signaling and reduces sensitivity to oxaliplatin/fluorouracil, providing a potential molecular target for CRC therapy.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Abstract

Introduction

Single-cell RNA sequencing in CRC

Multiomics analyses and AKT pathway activation

MDFI function and relevance to CRC

CANCER BIOLOGY & THERAPY 2024, VOL. 25, NO. 1, 2314324 [https://doi.org/10.1080/15384047.2024.2314324](https://doi.org/10.1080/15384047.2024.2314324) RESEARCH PAPER MDFI promotes the proliferation and tolerance to chemotherapy of colorectal cancer cells by binding ITGB4/LAMB3 to activate the AKT signaling pathway Ding Ma a,b\#, Shuwen Liua\#, Kua Liua\#, Lingkai Konga, Lingjun Xiaoa, Qilei Xinc, Chunping Jianga,c*, and Junhua Wua,c* aState Key Laboratory of Pharmaceutical Biotechnology, National Institute of Healthcare Data Science at Nanjing University, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, Jiangsu, China; bDepartment of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China; cJinan Microecological Biomedicine Shandong Laboratory, Shounuo City Light West Block, Jinan City, Shandong Province, China ABSTRACT Colorectal 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. ARTICLE HISTORY Received 21 September 2023 Revised 27 January 2024 Accepted 31 January 2024 KEYWORDS scRNA-seq (single-cell RNA sequencing); PPIs (proteinprotein interactions); MDFI (MyoD family inhibitor); ITGB4/LAMB3; AKT Introduction Colorectal cancer (CRC) is one of the most common malignant digestive tract cancers in the world. CRC accounts for approximately 1/10 of all tumor deaths. 1 An in-depth analysis of the potential mechanism of CRC occurrence and development is urgent and essential for the development of effective therapeutic targets and new clinical treatment strategies. Single-cell RNA sequencing (scRNA-seq) has enabled the systematic study of all kinds of human diseases, especially for tumors.2,3 Wang et al. discovered that cancer epithelial cells are important in tumor CRC progression, and key targets correlated with the prognosis ofCRC have been found via single-cell RNA sequencing (scRNA-seq) .4 The molecular landscapes and phenotypes of CRC have been revealed through extensive multiomics studies.5,6 The scRNA-seq method revealed the dynamic relationships among cellular components and the diversity of their functions, and CRC molecular subtypes were determined by scRNA-seq.7,8 To reveal an unbiased mechanism resulting in CRC tumorigenesis and development, we performed detailed analyses ofscRNA-seq data from the GSE144735 dataset. The differentially expressed genes between normal epithelial cells and tumors were identified. Pathway analyses were then performed to identify pathways that were enriched in DEGs, after which we used WGCNA to identify the gene group (module) that had the strongest pathway correlation. Finally, we ide

FAQs

What is the main finding about MDFI in colorectal cancer cells?

MDFI promotes colorectal cancer cell proliferation and increases tolerance to chemotherapy. The study links these effects to activation of the AKT signaling pathway through ITGB4/LAMB3 binding.

How did the study analyze AKT pathway activation?

AKT pathway activation was analyzed using KEGG with single-cell sequencing data from the GSE144735 dataset, then evaluated through correlations and protein-protein interaction analyses and verified with TCGA and CCLE datasets.

Which experiments support the mechanistic role of MDFI?

The mechanistic role was validated using coimmunoprecipitation, knockdown, and lentiviral overexpression experiments. Drug sensitivity was tested with colony formation and CCK8 assays.

Sep 22, 2026

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