Increased HSF1 Promotes Infiltration and Metastasis in Cervical Cancer via Enhancing MTDH-VEGF-C Expression.
Increased HSF1 Promotes Infiltration and Metastasis in Cervical Cancer via Enhancing MTDH-VEGF-C Expression.
复制标题
HSF1 增加通过增强 MTDH-VEGF-C 表达促进宫颈癌的浸润和转移。
DOI：
10.2147/ott.s291812
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发表时间：
2021
影响因子：
4
通讯作者：
Xiao X
中科院分区：
文献类型：
--
作者：
Shi X;Deng Z;Wang S;Zhao S;Xiao L;Zou J;Li T;Tan S;Tan S;Xiao X
探讨HSF1在体内外促进宫颈癌的分子机制。采用免疫组化方法检测110例不同分级宫颈癌石蜡包埋切片中HSF1的表达。免疫组化分析HSF1下游靶点Metadherin （MTDH）、VEGF-C和CD31的表达。采用EMSA、CHIP和荧光素酶检测HSF1在MTDH启动子区域的转录活性。MTT法和克隆形成法检测细胞增殖和克隆性。采用划痕分析和transwell实验考察细胞的迁移和侵袭能力。在异种移植模型中检测hsf1介导的体内肿瘤发生。宫颈癌细胞系中HSF1的表达明显高于正常人宫颈组织。HSF1增强了MTDH、VEGF-C和CD31的表达。HSF1可与MTDH启动子结合，促进MTDH的表达。HSF1增强HeLa细胞增殖和克隆形成。此外，HSF1增加了HeLa细胞在体外的迁移和侵袭。在移植瘤模型中，HSF1干扰后抑制体内肿瘤生长，降低MTDH、VEGF-C和CD31的表达。HSF1可促进宫颈癌的增殖、转移和侵袭。
To explore the molecular mechanism of promoting cervical cancer by HSF1 in vivo and in vitro. The expression of HSF1 in 110 paraffin-embedded cervical cancer sections of different grades was examined via immunohistochemistry analyses. Expression of HSF1 downstream targets Metadherin (MTDH), VEGF-C and CD31 were studied using immunohistochemistry analyses. HSF1 transcriptional activity in the MTDH promoter region was detected by EMSA, CHIP and luciferase. Cell proliferation and clonality were detected by MTT and clonal formation assay. Cell migration and invasion ability were investigated by scratch analysis and transwell assay. HSF1-mediated tumorigenesis in vivo was examined in xenograft models. HSF1 expression of cervical cancer cell line was increased compared to normal human cervical tissues. HSF1 enhanced the expression of MTDH, VEGF-C and CD31. HSF1 can combine with MTDH promoter to promote the expression of MTDH. HSF1 enhanced HeLa cell proliferation and clone formation. Furthermore, HSF1 increased HeLa cells migration and invasion in vitro. In the transplanted tumor model, HSF1 inhibited tumor growth in vivo after interference, and reduced the expression of MTDH, VEGF-C and CD31. HSF1 can promote the proliferation, metastasis and invasion of cervical cancer.