OncoTargets and Therapy (Feb 2021)
Increased HSF1 Promotes Infiltration and Metastasis in Cervical Cancer via Enhancing MTDH-VEGF-C Expression
Abstract
Xueyan Shi,1 Zhenghao Deng,2 Shouman Wang,3 Shuai Zhao,1,4 Lan Xiao,5 Jiang Zou,1 Tao Li,1 Sichuang Tan,6 SipAin Tan,1 Xianzhong Xiao1 1Sepsis Translational Medicine, Key Laboratory of Hunan Province, Xiangya School of Medicine, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 2Department of Pathology, Xiangya School of Medicine, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 3Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 4Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People’s Republic of China; 5Department of Traditional Chinese Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 6Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of ChinaCorrespondence: SipAin Tan Tel +86 – 13975805079Email [email protected] Tan Tel +86 – 13975806723Email [email protected]: To explore the molecular mechanism of promoting cervical cancer by HSF1 in vivo and in vitro.Methods: 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.Results: 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.Discussion: HSF1 can promote the proliferation, metastasis and invasion of cervical cancer.Keywords: HSF1, cervical cancer tissue, metastasis, MTDH, transcriptional regulation
