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您的检索式：作者名="Shuntai Chen"
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| 1 | IGF-1R inhibition induces MEK phosphorylation to promote survival in colon carcinomas显示文摘The insulin-like growth factor 1 receptor(IGF-1R)governs several signaling pathways for cell proliferation,survival,and antiapoptosis.Thus,targeting IGF-1R appears as a reasonable rationale for tumor treatment.However,clinical studies showed that inhibition of IGF-1R has very limited efficacy due to the development of resistance to IGF-1R blockade in tumor cells.Here,we discovered that prolonged treatment of colon cancer cells with IGF-1R inhibitors(BMS-754807 and GSK1838705A)stimulates p70 KDa ribosomal protein S6 kinase 1(p70S6K1)activation,a well-known kinase signaling for cell survival.We also found that p70S6K1 activation by IGF-1R inhibition is independent of K-Ras and PIK3CA mutations that frequently occur in colon cancer.Besides the increased p70S6K1 phosphorylation,the phosphorylation of mitogen-activated protein kinase kinase 1 and 2(MEK1/2)was elevated in the cells treated with BMS-754807.Interestingly,the increases in MEK1/2 and p70S6K1 phosphorylation were also observed when cells were subjected to the treatment of AKT inhibitor or genetic knockdown of AKT2 but not AKT1,suggesting that AKT2 inhibition stimulates MEK1/2 phosphorylation to activate p70S6K1.Conversely,inhibition of MEK1/2 by MEK1/2 inhibitor(U0126)or knockdown of MEK1 and MEK2 by corresponding mek1 and mek2 siRNA enhanced AKT phosphorylation,indicating mutual inhibition between AKT and MEK.Furthermore,the combination of BMS-754807 and U0126 efficiently decreased the cell viability and increased cleaved caspase 3 and apoptosis in vitro and in vivo.Our data suggest that the treatment of colon tumor cells with IGF-1R inhibitors stimulates p70S6K1 activity via MEK1/2 to promote survival,providing a new strategy for colorectal cancer therapeutics. | Qing Wang Yan Zhang Jiang Zhu Honggang Zheng Shuntai Chen Li Chen Hsin-Sheng Yang | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 2 |
| 2 | Effect of earlier initiation of antiretroviral treatment and increased treatment coverage on HIV-related mortality in China: a national observational cohort study显示文摘 | Fujie Zhang Zhihui Dou Ye Ma Yao Zhang Yan Zhao Decai Zhao Shuntai Zhou Marc Bulterys Hao Zhu Ray Y Chen | 2011 | The Lancet Infectious Diseases2011，，7： | 1 |
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