Increased HSF1 Promotes Infiltration and Metastasis in Cervical Cancer via Enhancing MTDH-VEGF-C Expression

Abstract

Purpose 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.

Geldanamycin ameliorates multiple organ dysfunction and microthrombosis in septic mice by inhibiting the formation of the neutrophil extracellular network by activating heat shock factor 1 HSF1

“…Past studies have shown that HSF1 reduced macrophage infiltration by inhibiting the transcription of monocyte chemoattractant protein‐1 (MCP‐1)/chemokine (C‐C motif) receptor 2 (CCR2) and attenuated LPS‐induced acute liver injury in mice 37 . In addition, HSF1 promoted the proliferation, metastasis and invasion of cervical cancer by promoting the expression of MTDH via binding to the MTDH promoter 38 . In sepsis, HSF1 exerted a protective role against multiple organ dysfunction in sepsis by inhibiting coagulation activity and microthrombosis through direct upregulation of t‐PA 17 .…”

“…37 In addition, HSF1 promoted the proliferation, metastasis and invasion of cervical cancer by promoting the expression of MTDH via binding to the MTDH promoter. 38 In sepsis, HSF1 exerted a protective role against multiple organ dysfunction in sepsis by inhibiting coagulation activity and microthrombosis through direct upregulation of t-PA. 17 Interestingly, we found that GA ameliorated microthrombosis and coagulopathy in septic mice via the pathways described above, thereby ameliorating multiple organ dysfunction. This effect may be achieved by increasing the stability of the active HSF1 trimer.…”

HSF1 excludes CD8+ T cells from breast tumors via suppression of CCL5

“…3A-B). HSF1 has previously been associated with outcomes for many cancer types and the HAS reflected many of these known associations including liver (55,56), lung (57), pancreatic (58), melanoma (46), esophageal (48), cervical (59), and head/neck (60) cancers (Fig. 3A-B).…”

HSF1 Protects Sepsis-Induced Acute Lung Injury by Inhibiting NLRP3 Inflammasome Activation

“…Currently, only HSF1 has been reported in sepsis-related studies. HSF1 activation is regulated by a multimolecular chaperone complex composed of HSP40, HSP70, and HSP90 ( 13 , 30 ). It has been reported that inhibition of HSP70 expression may lead to dysfunction of immune cells and reduce resistance to infectious infection during severe sepsis.…”