中国肿瘤生物治疗杂志2025，Vol.32Issue(10)：1027-1035,9.DOI:10.3872/j.issn.1007-385x.2025.10.004
GZMM激活VEGF/ERK信号通路促进肾透明细胞癌血管生成和侵袭
GZMM promotes the angiogenesis and invasion of clear cell renal cell carcinoma by activating the VEGF/ERK signaling pathway
摘要
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.关键词
肾透明细胞癌/颗粒酶M/血管生成/VEGF/ERK信号通路/侵袭Key words
clear cell renal cell carcinoma(ccRCC)/granzyme M(GZMM)/angiogenesis/VEGF/ERK signaling pathway/invasion分类
临床医学引用本文复制引用
李巍,马柯,王文鑫,徐梓山,张硕,孙慧芳,贺国洋..GZMM激活VEGF/ERK信号通路促进肾透明细胞癌血管生成和侵袭[J].中国肿瘤生物治疗杂志,2025,32(10):1027-1035,9.基金项目
国家自然科学基金(No.81772524) （No.81772524）
