ERp57 modulates STAT3 activity in radioresistant laryngeal cancer cells and serves as a prognostic marker for laryngeal cancer.
ERp57 modulates STAT3 activity in radioresistant laryngeal cancer cells and serves as a prognostic marker for laryngeal cancer.
复制标题
DOI：
10.18632/oncotarget.3042
复制
发表时间：
2015-02-20
期刊：
影响因子：
--
通讯作者：
Kim JS
中科院分区：
文献类型：
--
作者：
Choe MH;Min JW;Jeon HB;Cho DH;Oh JS;Lee HG;Hwang SG;An S;Han YH;Kim JS
尽管靶向放射抗性肿瘤细胞对于增强放射治疗的疗效至关重要，但抗性肿瘤中激活的信号仍不清楚。本研究表明ERp57通过激活STAT3促进喉癌的放射抗性。 ERp57 增加与喉癌细胞的放射抗性表型相关。有趣的是，与对照细胞相比，在抗辐射细胞中观察到 ERp57 和 STAT3 之间的相互作用增强。这种物理复合物是激活抗辐射细胞中 STAT3 所必需的。在 STAT3 调节基因中，Mcl-1 主要受 ERp57 调节。用化学抑制剂抑制 STAT3 活性或 siRNA 介导的 Mcl-1 耗竭使放射抗性细胞对辐射敏感，表明 ERp57-STAT3-Mcl-1 轴调节喉癌细胞的放射抗性。此外，我们观察到 ERp57 与磷酸化 STAT3 或 Mcl-1 之间呈正相关，并且在人喉癌中观察到 ERp57 与 STAT3 之间的体内相互作用。重要的是，我们还发现 ERp57-STAT3 复合物的增加与人类喉癌的不良预后相关，表明 ERp57-STAT3 调节的预后作用。总体而言，我们的数据表明 ERp57-STAT3 调节在喉癌放射抵抗中发挥作用，靶向 ERp57-STAT3 通路可能对提高人类喉癌放射治疗的疗效很重要。
Although targeting radioresistant tumor cells is essential for enhancing the efficacy of radiotherapy, the signals activated in resistant tumors are still unclear. This study shows that ERp57 contributes to radioresistance of laryngeal cancer by activating STAT3. Increased ERp57 was associated with the radioresistant phenotype of laryngeal cancer cells. Interestingly, increased interaction between ERp57 and STAT3 was observed in radioresistant cells, compared to the control cells. This physical complex is required for the activation of STAT3 in the radioresistant cells. Among STAT3-regulatory genes, Mcl-1 was predominantly regulated by ERp57. Inhibition of STAT3 activity with a chemical inhibitor or siRNA-mediated depletion of Mcl-1 sensitized radioresistant cells to irradiation, suggesting that the ERp57-STAT3-Mcl-1 axis regulates radioresistance of laryngeal cancer cells. Furthermore, we observed a positive correlation between ERp57 and phosphorylated STAT3 or Mcl-1 and in vivo interactions between ERp57 and STAT3 in human laryngeal cancer. Importantly, we also found that increased ERp57-STAT3 complex was associated with poor prognosis in human laryngeal cancer, indicating the prognostic role of ERp57-STAT3 regulation. Overall, our data suggest that ERp57-STAT3 regulation functions in radioresistance of laryngeal cancer, and targeting the ERp57-STAT3 pathway might be important for enhancing the efficacy of radiotherapy in human laryngeal cancer.
登录
查看更多内容
影响因子：
11.2
作者：
Ding Q;Huo L;Yang JY;Xia W;Wei Y;Liao Y;Chang CJ;Yang Y;Lai CC;Lee DF;Yen CJ;Chen YJ;Hsu JM;Kuo HP;Lin CY;Tsai FJ;Li LY;Tsai CH;Hung MC
通讯作者：
Hung MC
影响因子：
3.6
作者：
Kim JS;Yun HS;Um HD;Park JK;Lee KH;Kang CM;Lee SJ;Hwang SG
通讯作者：
Hwang SG
影响因子：
12.4
作者：
Kim, JS;Park, ZY;Chun, JS
通讯作者：
Chun, JS
影响因子：
5.7
作者：
Liao, Chia-Jung;Wu, Tzu-I;Lin, Kwang-Huei
通讯作者：
Lin, Kwang-Huei
影响因子：
3.9
作者：
Chichiarelli, Silvia;Gaucci, Elisa;Eufemi, Margherita
通讯作者：
Eufemi, Margherita