中国病理生理杂志2025，Vol.41Issue(9)：1730-1737,8.DOI:10.3969/j.issn.1000-4718.2025.09.008
STIM1通过激活核糖体通路促进唾液腺腺样囊性癌迁移、侵袭及血管生成
STIM1 promotes migration,invasion and angiogenesis of salivary ade-noid cystic carcinoma by activating ribosomal pathway
摘要
Abstract
AIM:To explore the role of stromal interaction molecule 1(STIM1)in the migration,invasion and angiogenesis of salivary adenoid cystic carcinoma(SACC),as well as its molecular mechanism.METHODS:Immu-nohistochemistry and Western blot were used to detect the expression level of STIM1 in human SACC tumor tissues and ad-jacent normal tissues.The TCGA database was analyzed to investigate the relationship between STIM1 expression and sur-vival in patients.A SACC-83 cell line with stable STIM1 overexpression(STIM1-OE)was established and divided into two groups:blank control(STIM1-Vec)group and STIM1-OE group.A nude mouse subcutaneous xenograft tumor model(n=6)was used to detect SACC growth.Transwell chamber assay,scratch test and dorsal root ganglion model were ap-plied to assess SACC migration and invasion.Immunohistochemistry was performed to detect the expression of CD34 and STIM1 in tumor tissues of nude mice.A nude mouse Matrigel plug model and human umbilical vein endothelial cell(HUVEC)tube formation assay were used to evaluate angiogenesis.Enzyme linked immunosorbent assay was employed to detect the levels of vascular endothelial growth factor(VEGF)and epidermal growth factor(EGF)in cell culture supernatants.RT-qPCR and Western blot were performed to detect the mRNA and protein expression levels of c-Myc,ribosomal protein L35(RPL35),ribosomal protein SA(RPSA),mitochondrial ribosomal protein L11(RPL11)and FAU ubiquitin like and ribo-somal protein S30 fusion(FAU).The STIM1-siRNA and RPL35-siRNA were transfected into SACC-83 cells,and the mi-gration,invasion and angiogenesis abilities of the cells were detected using the same methods as above.RESULTS:STIM1 was highly expressed in SACC,and the patients with high STIM1 expression had shorter survival time.In vivo,compared with STIM1-Vec group,STIM1-OE promoted tumor growth.In vitro,the number of migrating and invading SACC cells in STIM1-OE group was significantly increased,and the nerve invasion ability was also significantly en-hanced.Conversely,STIM1-siRNA significantly reduced the migration and invasion abilities of SACC cells.Additional-ly,STIM1-OE significantly promoted the expression of the vascular marker CD34,the secretion of VEGF and EGF,and the results of Matrigel plug and HUVEC tube formation assays indicated that STIM1-OE significantly promoted angiogene-sis.Silencing of RPL35 significantly inhibited SACC migration,invasion,and angiogenesis.RT-qPCR and Western blot results showed that the mRNA levels of RPL35,RPSA,MRPL11 and FAU were significantly increased(P<0.05),and the protein expression levels of STIM1,c-Myc and RPL35 were significantly increased(P<0.01).CONCLUSION:STIM1 drive the migration,invasion and angiogenesis of SACC by activating c-Myc/RPL35-mediated ribosome pathway.关键词
唾液腺腺样囊性癌/基质相互作用分子1/核糖体通路/细胞迁移/肿瘤侵袭/血管新生Key words
salivary adenoid cystic carcinoma/stromal interaction molecule 1/ribosome pathway/cell migra-tion/tumor invasion/angiogenesis分类
医药卫生引用本文复制引用
刘唐君,程晓婷,岳红叶,刘佳璐,李厚君,孙志朋,柳云霞..STIM1通过激活核糖体通路促进唾液腺腺样囊性癌迁移、侵袭及血管生成[J].中国病理生理杂志,2025,41(9):1730-1737,8.基金项目
国家自然科学基金资助项目(No.82204391) （No.82204391）
山东医药卫生项目(No.202408020545) （No.202408020545）
潍坊医学院公派国内访学项目(No.20237-24) （No.20237-24）
