Targeting valosin‐containing protein enhances the efficacy of radiation therapy in esophageal squamous cell carcinoma. Issue 11 (13th September 2019)

• Record Type: Journal Article
• Authors: Luo, Hui; Song, Hengli; Mao, Ronghu; Gao, Qiang; Feng, Zhuo; Wang, Nan; Song, Shuai; Jiao, Ruidi; Ni, Peizan; Ge, Hong
• Is Part Of: Cancer science. Volume 110:Issue 11(2019)
• Page Start: 3464
• Page End: 3475
• Publication Date: 2019-09-13
• Subjects: endoplasmic reticulum stress -- esophageal squamous cell carcinoma -- prognosis -- radiation resistance -- valosin‐containing protein; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.14184
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract: Overcoming resistance to radiation is a great challenge in cancer therapy. Here, we highlight that targeting valosin‐containing protein (VCP) improves radiation sensitivity in esophageal squamous cell carcinoma (ESCC) cell lines and show the potential of using VCP as a prognosis marker in locally advanced ESCC treated with radiation therapy. Esophageal squamous cell carcinoma cell lines with high VCP expression were treated with VCP inhibitor combined with radiotherapy. Cell proliferation, colony formation, cell death, and endoplasmic reticulum (ER) stress signaling were evaluated. Moreover, patients with newly diagnosed locally advanced ESCC who were treated with radiotherapy were analyzed. Immunohistochemistry was used to detect the expression of VCP. The correlation between overall survival and VCP was investigated. Esophageal squamous cell carcinoma cells treated with VCP inhibitor and radiotherapy showed attenuated cell proliferation and colony formation and enhanced apoptosis. Further investigation showed this combined strategy activated the ER stress signaling involved in unfolded protein response, and inhibited the ER‐associated degradation (ERAD) pathway. Clinical analysis revealed a significant survival benefit in the low VCP expression group. Targeting VCP resulted in antitumor activity and enhanced the efficacy of radiation therapy in ESCC cells in vitro. Valosin‐containing protein is a promising and novel target. In patients with locally advanced ESCC who received radiotherapy, VCP can be considered as a useful prognostic indicator of overall survival. Valosin‐containing protein inhibitors could be developed for use as effective cancer therapies, in combination with radiation therapy. Abstract : Targeting valosin‐containing protein (VCP) offers a new strategy in enhancing radiation sensitivity. An elevated expression of VCP is associated with unfavorable survival in locally advanced esophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy. Valosin‐containing protein expression has the potential to be used as an independent prognostic factor in ESCC.