14-3-3σ confers cisplatin resistance in esophageal squamous cell carcinoma cells via regulating DNA repair molecules

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
Kenneth K Y LaiSimon Law

Abstract

Esophageal squamous cell carcinoma (ESCC) is the predominant type of esophageal cancer in Asia. Cisplatin is commonly used in chemoradiation for unresectable ESCC patients. However, the treatment efficacy is diminished in patients with established cisplatin resistance. To understand the mechanism leading to the development of cisplatin resistance in ESCC, we compared the proteomes from a cisplatin-resistant HKESC-2R cell line with its parental-sensitive counterpart HKESC-2 to identify key molecule involved in this process. Mass spectrometry analysis detected 14-3-3σ as the most abundant molecule expressed exclusively in HKESC-2R cells, while western blot result further validated it to be highly expressed in HKESC-2R cells when compared to HKESC-2 cells. Ectopic expression of 14-3-3σ increased cisplatin resistance in HKESC-2 cells, while its suppression sensitized SLMT-1 cells to cisplatin. Among the molecules involved in drug detoxification, drug transportation, and DNA repair, the examined DNA repair molecules HMGB1 and XPA were found to be highly expressed in HKESC-2R cells with high 14-3-3σ expression. Subsequent manipulation of 14-3-3σ by both overexpression and knockdown approaches concurrently altered the expression of HM...Continue Reading

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Citations

Jan 25, 2018·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Lai Nar TungNikki P Lee
Oct 22, 2019·Future Medicinal Chemistry·Tiantian ZhangChanghu Xue
Sep 21, 2020·Clinica Chimica Acta; International Journal of Clinical Chemistry·Yun HuangWeiguo Huang

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