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Updated: Jun 5, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

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Key Regulatory Elements of the TGFβ-LRRC15 Axis Predict Disease Progression and Immunotherapy Resistance Across

Claire M Storey, Michael Cheng, Mohamed Altai

    Biorxiv : the Preprint Server for Biology
    |December 9, 2024
    PubMed

    Insights

    Transforming growth factor-beta (TGFβ) drives cancer progression by upregulating LRRC15. Identifying key genes like MMP2 and SPARC offers new immunotherapy targets for better cancer treatment.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Immunology

    Background:

    • Transforming growth factor-beta (TGFβ) exhibits complex roles in cancer, initially tumor-suppressive but later promoting metastasis and immune evasion.
    • Targeting TGFβ is challenging due to toxicity and broad immunosuppression.
    • Leucine-rich repeat-containing protein 15 (LRRC15) is a TGFβ-regulated antigen found on cancer cells and cancer-associated fibroblasts (CAFs), with its precise regulation by TGFβ being unclear.

    Purpose of the Study:

    • To elucidate the molecular mechanisms by which TGFβ upregulates LRRC15 expression.
    • To identify key genomic regulators involved in TGFβ-induced LRRC15 expression.
    • To explore the potential of identified genes in predicting immunotherapy response.

    Main Methods:

    • Integrated functional compound screening and single-cell RNA sequencing.
    • Construction of gene regulatory networks.
    • Validation in cell models.

    Main Results:

    • Identified key genomic features regulating TGFβ-induced LRRC15 expression.
    • Gene regulatory network analysis pinpointed MMP2, SPARC, TGFβR2, and WNT5B as central regulators.
    • Validated the role of these genes in cell models.

    Conclusions:

    • MMP2, SPARC, TGFβR2, and WNT5B are key mediators of TGFβ-induced LRRC15 pathobiology.
    • These genes hold potential for refining immunotherapy strategies.
    • Further research may enable personalized co-treatment options for cancer patients.

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