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Archive > Volume 32 Issue 10 > 2025,32(10):1027-1035. DOI:10.3872/j.issn.1007-385X.2025.10.004 Prev Next
Basic Research
GZMM promotes the angiogenesis and invasion of clear cell renal cell carcinoma by activating the VEGF/ERK signaling pathway
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Abstract:
[Abstract] Objective: To explore the effects of granzyme M (GZMM) on the proliferation, invasion, migration, and angiogenesis of clear cell renal cell carcinoma (ccRCC) cells and the underlying molecular mechanisms. Methods: TCGA database and immunohistochemistry were used to analyze the expression of GZMM in ccRCC tissues and its correlation with clinicopathological features. CCK-8, Transwell, wound healing, and angiogenesis assays were used to detect the effects of GZMM on the proliferation, invasion, migration, and angiogenesis of ccRCC cells. Weston blot assay was employed to detect the effects of GZMM on the VEGF/ ERK signaling pathway. Results: TCGA database and immunohistochemical analysis showed that the expression of GZMM in ccRCC tissues was elevated (P < 0.01), and was correlated with Fuhrman grading and lymph node metastasis (both P < 0.05). Patients with high expression of GZMM had a poor prognosis (P < 0.05), and it was associated with FcerⅠ-mediated MAPK activation (P < 0.001). In ccRCC cells, knockdown of GZMM decreased the proliferation, invasion and migration abilities and inhibited ERK signaling pathway (both P < 0.05) while overexpression of GZMM promoted the proliferation, invasion and migration abilities and activated ERK signaling pathway (both P < 0.01). In HUVECs, secreted GZMM promoted the proliferation, migration, tubule formation and angiogenesis abilities of HUVECs and activated VEGF/ERK signaling pathway (both P < 0.05). Furthermore, U0126 inhibited the expressions of p-ERK, MMP2, and MMP9 (all P < 0.05), but did not affect the expressions of VEGFA and VEGFR2. Conclusion: The expression of GZMM was elevated in ccRCC tissues and was correlated with its Fuhrman grading and lymph node metastasis. GZMM promoted the angiogenesis and invasion of ccRCC by activating VEGF/ERK signaling pathway.
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