High mobility group box 1 promotes radioresistance in esophageal squamous cell carcinoma cell lines by modulating autophagy.

Abstract	Resistance to radiotherapy results in relapse and treatment failure in locally advanced esophageal squamous cell carcinoma (ESCC). High mobility group box 1 (HMGB1) is reported to be associated with the radioresistance in bladder and breast cancer. However, the role of HMGB1 in the radiotherapy response in ESCC has not been fully elucidated. Here, we investigated the role of HMGB1 to radioresistance in ESCC clinical samples and cell lines. We found that HMGB1 expression was associated with tumor recurrence after postoperative radiotherapy in locally advanced ESCC patients. HMGB1 knockdown in ESCC cells resulted in increased radiosensitivity both in vitro and in vivo. Autophagy level was found depressed in HMGB1 inhibition cells and activation of autophagy brought back cell's radioresistance. Our results demonstrate that HMGB1 activate autophagy and consequently promote radioresistance. HMGB1 may be used as a predictor of poor response to radiotherapy in ESCC patients. Our finding also highlights the importance of the utility of HMGB1 in ESCC radiosensitization.
Authors	Hongbing Ma, Shuyu Zheng, Xiaozhi Zhang, Tuotuo Gong, Xin Lv, Shenbo Fu, Shuqun Zhang, Xiaoran Yin, Jingcan Hao, Changyou Shan, Shan Huang
Journal	Cell death & disease (Cell Death Dis) Vol. 10 Issue 2 Pg. 136 (02 12 2019) ISSN: 2041-4889 [Electronic] England
PMID	30755598 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	HMGB1 Protein HMGB1 protein, human RNA, Small Interfering
Topics	Adult Aged Animals Autophagy Cell Line, Tumor Esophageal Neoplasms (pathology, radiotherapy, surgery) Esophageal Squamous Cell Carcinoma (pathology, radiotherapy, surgery) Female Gene Knockdown Techniques HMGB1 Protein (genetics, metabolism) Heterografts Humans Male Mice Mice, Inbred BALB C Mice, Nude Middle Aged Neoplasm Recurrence, Local Prognosis RNA, Small Interfering (genetics) Radiation Tolerance (genetics) Transfection Tumor Burden (genetics)

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