JAK-STAT(janus tyrosine kinase-signal transducer and activator of transcription)细胞信号转导途径的紊乱,是肿瘤发生最重要的原因之一.近年来的研究发现,STAT-3作为JAK-STAT信号转导途径中一个重要的调节分子,能够通过将信号直接...JAK-STAT(janus tyrosine kinase-signal transducer and activator of transcription)细胞信号转导途径的紊乱,是肿瘤发生最重要的原因之一.近年来的研究发现,STAT-3作为JAK-STAT信号转导途径中一个重要的调节分子,能够通过将信号直接转导入细胞核而快速激活下游基因,从而保证相应配体顺利完成信号转导过程.然而,STAT-3也有其"黑暗"的一面,其往往在恶性肿瘤细胞中表现为持续活化,作为一种原癌基因,成为肿瘤治疗的新靶标.因而,对近年来有关STAT-3的持续活化与恶性肿瘤细胞的侵袭、转移过程及肿瘤干细胞的关系作一概述,有助于深入了解STAT-3在肿瘤发生发展机制中发挥的作用.展开更多
AIM:To investigate the correlation between gastric cancer growth and signal transducer and activator of transcription-3(STAT3) expression.METHODS:We assessed the expressions of STAT3,phosphor-STAT3(pSTAT3),suppressor ...AIM:To investigate the correlation between gastric cancer growth and signal transducer and activator of transcription-3(STAT3) expression.METHODS:We assessed the expressions of STAT3,phosphor-STAT3(pSTAT3),suppressor of cytokine signaling-1(SOCS-1),survivin and Bcl-2 in gastric cancer patients after gastrectomy by immunohistochemical method.In addition,in situ hybridization was used to further demonstrate the mRNA expression of STAT3 in gastric cancer.RESULTS:With the univariate analysis,expressions of STAT3,pSTAT3,SOCS-1,survivin and Bcl-2,the size of primary tumor and the lymph node metastasis were found to be associated with the overall survival(OS) of gastric cancer patients.However,only pSTAT3 expression and the lymph node metastasis were identified as the independent factors of OS of gastric cancer with multivariate analysis.STAT3 expression was correlated with the lymph node metastasis.There were positive correlations between expressions of STAT3,survivin,Bcl-2 and pSTAT3 in gastric cancer,whereas there was negative correlation between STAT3 expression and SOCS-1 expression in gastric cancer.CONCLUSION:STAT3 can transform into pSTAT3 to promote the survival and inhibit the apoptosis of gastric cancer cells.SOCS-1 might be the valid molecular antagonist to inhibit the STAT3 expression in gastric cancer.展开更多
Insulin-like growth factor binding protein-3 (IGFBP-3), a secretory protein, is the most abundant IGF binding protein present in human serum among all IGF binding proteins. IGFBP-3 shows decreased level of expression ...Insulin-like growth factor binding protein-3 (IGFBP-3), a secretory protein, is the most abundant IGF binding protein present in human serum among all IGF binding proteins. IGFBP-3 shows decreased level of expression in cancerous cells but has been known to be present in significant amounts in normal or non-cancerous cells. IGFBP-3 can induce apoptosis in prostate cancer cells either in an IGF-dependent manner or independently of IGF binding. Although putative cell death specific Insulin-like growth factor binding protein-3 (IGFBP-3R) receptor(s) has recently been identified by which IGFBP-3 may induce its anti-tumor effects, IGFBP-3 has also been known to activate various downstream intracellular signaling molecules via a different mechanistic pathway. Stat-1 has been known to be one of the candidate molecules activated by IGFBP-3. IGFBP-3 can also inhibit Akt/IGF-1 survival pathway in MCF-7 breast cancer cells which ultimately leads to the induction of apoptosis in these cells. All these studies clearly demonstrate that IGFBP-3 regulates cell proliferation and promotes its pro-apoptotic effects in cancer cells in two different pathways: 1) sequester IGF-I to bind to IGF-I receptor to inhibit cell proliferation and induce apoptosis, 2) independent of IGF-I pathway, IGFBP-3 binds to some putative receptor and activate various downstream pro-apoptotic molecules involved in cell death.展开更多
文摘JAK-STAT(janus tyrosine kinase-signal transducer and activator of transcription)细胞信号转导途径的紊乱,是肿瘤发生最重要的原因之一.近年来的研究发现,STAT-3作为JAK-STAT信号转导途径中一个重要的调节分子,能够通过将信号直接转导入细胞核而快速激活下游基因,从而保证相应配体顺利完成信号转导过程.然而,STAT-3也有其"黑暗"的一面,其往往在恶性肿瘤细胞中表现为持续活化,作为一种原癌基因,成为肿瘤治疗的新靶标.因而,对近年来有关STAT-3的持续活化与恶性肿瘤细胞的侵袭、转移过程及肿瘤干细胞的关系作一概述,有助于深入了解STAT-3在肿瘤发生发展机制中发挥的作用.
基金Supported by National Basic Research Program of China(973 Program),No.2010CB529301Tianjin Health Bureau Research Foundation,No.09KC74
文摘AIM:To investigate the correlation between gastric cancer growth and signal transducer and activator of transcription-3(STAT3) expression.METHODS:We assessed the expressions of STAT3,phosphor-STAT3(pSTAT3),suppressor of cytokine signaling-1(SOCS-1),survivin and Bcl-2 in gastric cancer patients after gastrectomy by immunohistochemical method.In addition,in situ hybridization was used to further demonstrate the mRNA expression of STAT3 in gastric cancer.RESULTS:With the univariate analysis,expressions of STAT3,pSTAT3,SOCS-1,survivin and Bcl-2,the size of primary tumor and the lymph node metastasis were found to be associated with the overall survival(OS) of gastric cancer patients.However,only pSTAT3 expression and the lymph node metastasis were identified as the independent factors of OS of gastric cancer with multivariate analysis.STAT3 expression was correlated with the lymph node metastasis.There were positive correlations between expressions of STAT3,survivin,Bcl-2 and pSTAT3 in gastric cancer,whereas there was negative correlation between STAT3 expression and SOCS-1 expression in gastric cancer.CONCLUSION:STAT3 can transform into pSTAT3 to promote the survival and inhibit the apoptosis of gastric cancer cells.SOCS-1 might be the valid molecular antagonist to inhibit the STAT3 expression in gastric cancer.
文摘Insulin-like growth factor binding protein-3 (IGFBP-3), a secretory protein, is the most abundant IGF binding protein present in human serum among all IGF binding proteins. IGFBP-3 shows decreased level of expression in cancerous cells but has been known to be present in significant amounts in normal or non-cancerous cells. IGFBP-3 can induce apoptosis in prostate cancer cells either in an IGF-dependent manner or independently of IGF binding. Although putative cell death specific Insulin-like growth factor binding protein-3 (IGFBP-3R) receptor(s) has recently been identified by which IGFBP-3 may induce its anti-tumor effects, IGFBP-3 has also been known to activate various downstream intracellular signaling molecules via a different mechanistic pathway. Stat-1 has been known to be one of the candidate molecules activated by IGFBP-3. IGFBP-3 can also inhibit Akt/IGF-1 survival pathway in MCF-7 breast cancer cells which ultimately leads to the induction of apoptosis in these cells. All these studies clearly demonstrate that IGFBP-3 regulates cell proliferation and promotes its pro-apoptotic effects in cancer cells in two different pathways: 1) sequester IGF-I to bind to IGF-I receptor to inhibit cell proliferation and induce apoptosis, 2) independent of IGF-I pathway, IGFBP-3 binds to some putative receptor and activate various downstream pro-apoptotic molecules involved in cell death.
