Tong Zhuting, Fang Weiyang, Xu Meng, Xia YeYe, Wang Rui, Li Yue, Zha Tianqi, Xiao Liang, Pan Shuhao, Chai Huiping, Zhao Lei, Wang Hao, Pan Huaguang, Chen Xiangcun
Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Department of Electrocardiography, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Cancer Cell Int. 2022 Mar 5;22(1):106. doi: 10.1186/s12935-022-02535-9.
Disabled homolog 2 interacting protein (DAB2IP) plays a tumor-suppressive role in several types of human cancers. However, the molecular status and function of the DAB2IP gene in esophageal squamous cell carcinoma (ESCC) patients who received definitive chemoradiotherapy is rarely reported.
We examined the expression dynamics of DAB2IP by immunohistochemistry (IHC) in 140 ESCC patients treated with definitive chemoradiotherapy. A series of in vivo and in vitro experiments were performed to elucidate the effect of DAB2IP on the chemoradiotherapy (CRT) response and its underlying mechanisms in ESCC.
Decreased expression of DAB2IP in ESCCs correlated positively with ESCC resistance to CRT and was a strong and independent predictor for short disease-specific survival (DSS) of ESCC patients. Furthermore, the therapeutic sensitivity of CRT was substantially increased by ectopic overexpression of DAB2IP in ESCC cells. In addition, knockdown of DAB2IP dramatically enhanced resistance to CRT in ESCC. Finally, we demonstrated that DAB2IP regulates ESCC cell radiosensitivity through enhancing ionizing radiation (IR)-induced activation of the ASK1-JNK signaling pathway.
Our data highlight the molecular etiology and clinical significance of DAB2IP in ESCC, which may represent a new therapeutic strategy to improve therapy and survival for ESCC patients.
Disabled同源物2相互作用蛋白（DAB2IP）在多种人类癌症中发挥肿瘤抑制作用。然而，关于接受根治性放化疗的食管鳞状细胞癌（ESCC）患者中DAB2IP基因的分子状态和功能的报道很少。
我们通过免疫组织化学（IHC）检测了140例接受根治性放化疗的ESCC患者中DAB2IP的表达动态。进行了一系列体内和体外实验，以阐明DAB2IP对ESCC放化疗（CRT）反应的影响及其潜在机制。
ESCC中DAB2IP表达降低与ESCC对CRT的耐药性呈正相关，并且是ESCC患者疾病特异性生存期（DSS）缩短的一个强有力的独立预测指标。此外，ESCC细胞中DAB2IP的异位过表达显著提高了CRT的治疗敏感性。此外，敲低DAB2IP显著增强了ESCC对CRT的耐药性。最后，我们证明DAB2IP通过增强电离辐射（IR）诱导的ASK1-JNK信号通路激活来调节ESCC细胞的放射敏感性。
我们的数据突出了DAB2IP在ESCC中的分子病因学和临床意义，这可能代表了一种改善ESCC患者治疗和生存的新治疗策略。
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