CTSG Suppresses Breast Cancer Progression by Inhibiting the EGFR/ERK Signaling Pathway and Enhancing CD8&#x207a; T Cell Activation.

Yue Pan; Chenhui Zheng; Danni Zheng; Yin Pan

doi:10.1016/j.clbc.2026.07.027

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CTSG Suppresses Breast Cancer Progression by Inhibiting the EGFR/ERK Signaling Pathway and Enhancing CD8⁺ T Cell Activation.

Yue Pan·Chenhui Zheng·Danni Zheng·Yin Pan

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Abstract

BACKGROUND: Breast cancer (BC), the most common female malignancy, has metastasis as its main cause of mortality. Cathepsin G (CTSG) is involved in tumorigenesis and immunity. This study explores the role of CTSG in BC progression and CD8 + T cell regulation. METHODS: Differentially expressed genes and proteins (DEGs/DEPs) were analyzed using Limma, and core genes were screened using Random Forest (RF) and Least absolute shrinkage and selection operator (LASSO). CTSG expression was analyzed using GSE36295, the Cancer Genome Atlas (TCGA), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blot. Cell viability, proliferation, cell cycle, migration, and invasion were detected using Cell Counting Kit-8 (CCK8), 5‑Ethynyl‑2'‑deoxyuridine (EdU), flow cytometry, and Transwell assays, respectively. Sphere diameter was analyzed via sphere formation assay. Downstream mechanisms were examined using western blot, CCK8, flow cytometry, and Transwell assays. CD8 + T cell activity was examined using EdU, western blot, and flow cytometry. RESULTS: A total of 177 genes overlapped between GSE36295 DEGs and PDC000173 DEPs. CTSG was the hub gene identified by RF and LASSO. CTSG expression was significantly reduced in BC (P < 0.01). CTSG overexpression suppressed cell viability, proliferation, migration, invasion, sphere formation, and CD44 and CD133 expression (P < 0.01). CTSG up-regulation inhibited epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinase (ERK) signaling axis and reduced cancer cell malignancy (P < 0.01). CTSG overexpression activated CD8 + T cells via EGFR/ERK inhibition, enhancing their cytotoxic effect on cancer cells (P < 0.01). CONCLUSION: CTSG inhibits BC malignancy and enhances CD8 + T cell function via EGFR/ERK inhibition.

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Humans Female Breast Neoplasms CD8-Positive T-Lymphocytes ErbB Receptors Cell Proliferation MAP Kinase Signaling System Disease Progression Cell Movement Gene Expression Regulation, Neoplastic Lymphocyte Activation Cell Line, Tumor Cathepsin G Immunomodulation Mammary neoplasms Serine proteases Tumor progression Journal Article

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Yue Pan, Chenhui Zheng, Danni Zheng, Yin Pan. 2026-07-26. CTSG Suppresses Breast Cancer Progression by Inhibiting the EGFR/ERK Signaling Pathway and Enhancing CD8⁺ T Cell Activation.. https://doi.org/10.1016/j.clbc.2026.07.027

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