期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 165, 期 -, 页码 348-359出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2021.01.056
关键词
Esophageal squamous cell carcinoma; Syntaphilin; Mitochondrial distribution; Invasion; Radioresistance
资金
- National Natural Science Foundation of China [81773228, 81902539]
This study indicates that low expression of SNPH is a novel indicator of radioresistance in ESCC, and targeting SNPH could be a promising approach to enhance radiotherapeutic efficiency in patients with ESCC.
Syntaphilin (SNPH) halts mitochondrial movements and regulates proliferation-motility phenotype switching of cancer cells. We sought to investigate the significance of SNPH-mediated mitochondria distribution in radio resistant (RR) phenotype switching in esophageal squamous cell carcinoma (ESCC). RR ESCC cells were established by long-term exposure to radiation. Effects of SNPH on proliferation, migration, mitochondrial distribution, radiation-induced oxidative damage and radiosensitivity were investigated by overexpressing or silencing SNPH. The mechanisms regulating SNPH expression and the potential molecules mediating the SNPHre-expression-induced radiosensitization were explored. SNPH expression in specimens from 156 patients was analyzed to evaluate its clinical significance. We found that RR ESCC cells had a sparse mitochondrial network and lower SNPH level. SNPH reconstitution in RR ESCC cells inhibited migration, induced proliferation and mitochondrial aggregation, exacerbated the radiation-induced oxidative damage and ultimately promoted radiosensitization. Mechanistically, ubiquitin-proteasomal degradation and histone modification contributed to SNPH downregulation in RR ESCC cells. Subsequently, we found that CREB dephosphorylation facilitated the SNPH re-expression-induced radiosensitization. Furthermore, SNPH expression was correlated with the radio therapeutic efficacy and served as an independent prognostic factor for survival of ESCC patients. Our study revealed that low SNPH expression was a novel indicator for radioresistance, and targeting SNPH could be a promising regimen to improve the radiotherapeutic efficiency in ESCC patients.
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