ESM1/VEGFα/ERK signaling axis augments cell proliferation and tumor angiogenesis in human cervical squamous cell carcinoma

Abstract

Abstract Background Aberrant expression of endothelial cell specific molecule 1 (ESM1) is frequent in the carcinogenesis of various neoplasms. However, the expression profile and prognostic value of ESM1 in CSCC remain ill-defined. Methods Human specimens were utilized to investigate the expression of ESM1 in normal cervical tissue, LSIL, HSIL, and CSCC samples by IHC and RT-qPCR assay. And, it was further validated and explored in CSCC based on GEO and TCGA datasets. Then, genomic enrichment analysis (GSEA) and in vitro experiments of human CSCC cell lines, including SiHa and ME-180, were applied to probe the potential molecular mechanisms of ESM1 in CSCC. Results In human samples, the ESM1 was hyper-expressed in CSCC, compared with the normal ones. Combined with TCGA and GEO, it further revealed that ESM1 was significantly overexpressed and related to dismal prognosis in CSCC patients. And, GSEA analysis showed that the tumor angiogenesis and the VEGFα signaling pathway were mostly enriched in CSCC patients with ESM1 high expression. Then, the in vitro experiment suggested that interference of ESM1 inhibited cell proliferation, migration, invasion, and enhanced apoptosis, resulting in the reduction of VEGFα expression and the phosphorylation of VEGFR2 (P-VEGFR2) and ERK-1/2 (P-ERK-1/2) in SiHa and ME-180 cells. Conclusions ESM1 is notably overexpressed in CSCC patients. Overexpression of ESM1 predicts an adverse prognosis of CSCC. Overexpressed ESM1 augments tumor angiogenesis and progression of CSCC via the VEGFα/ERK signaling pathway. Thus, ESM1 and related genes may serve as promising prognostic biomarkers or candidate therapeutic targets for CSCC patients.