Int J Med Sci 2022; 19(6):1072-1081. doi:10.7150/ijms.71892 This issue

Research Paper

ETV5 overexpression promotes progression of esophageal squamous cell carcinoma by upregulating SKA1 and TRPV2

Ming-Chuang Sun1, Kang Fang1, Zhao-Xing Li1, Yuan Chu1, Ai-Ping Xu1, Zi-Ying Zhao1, Zhu-Yun Leng1, Yun-Wei Zhang1, Ze-Hua Zhang1, Li Zhang2, Tao Chen1✉, Mei-Dong Xu1✉

1. Endoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China
2. Department of Pathology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China
Ming-Chuang Sun and Kang Fang contributed equally to this work.

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Citation:
Sun MC, Fang K, Li ZX, Chu Y, Xu AP, Zhao ZY, Leng ZY, Zhang YW, Zhang ZH, Zhang L, Chen T, Xu MD. ETV5 overexpression promotes progression of esophageal squamous cell carcinoma by upregulating SKA1 and TRPV2. Int J Med Sci 2022; 19(6):1072-1081. doi:10.7150/ijms.71892. Available from https://www.medsci.org/v19p1072.htm

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Abstract

Graphic abstract

Esophageal squamous cell carcinoma (ESCC) is notorious for the rapid progression especially early tumor metastasis due to the unclear mechanism. Recently, ETV5 attracts much attention for its potential role as an oncogenic transcription factor involved in multiple cancers. However, no one reported the mechanism behind the association between ETV5 expression and esophageal squamous cell carcinoma progression. In this study, we found that ETV5 was upregulated in ESCC both from online database and our ESCC tissues and ETV5 was associated with tumor staging and prognosis. Knockdown of ETV5 or its downstream genes SKA1 and TRPV2 significantly suppress ESCC cells migration and invasion, respectively. Additionally, in vivo study showed knockdown of ETV5 inhibited tumor metastasis. Further experiments unveiled ETV5 could transcriptionally upregulate the expression of SKA1 and TRPV2 and further activate MMPs in ESCC progression. In conclusion, ETV5 was associated with ESCC tumor staging and ESCC prognosis clinically. ETV5 promoted metastasis of ESCC by activating MMPs through augmenting the transcription of SKA1 and TRPV2. ETV5 was likely to be a novel oncogene and therapeutic target in ESCC.

Keywords: Esophageal squamous cell carcinoma, ETV5, SKA1, TRPV2, MMPs, metastasis