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论文题目: A splicing isoform of TEAD4 attenuates the Hippo-YAP signalling to inhibit tumour proliferation
英文论文题目: A splicing isoform of TEAD4 attenuates the Hippo-YAP signalling to inhibit tumour proliferation
第一作者: Qi, YF; Yu, J; Han, W; Fan, XJ; Qian, HL; Wei, HH; Tsai, YHS; Zhao, JY; Zhang, WJ; Liu, QT; Meng, SS; Wang, Y; Wang, ZF
英文第一作者: Qi, YF; Yu, J; Han, W; Fan, XJ; Qian, HL; Wei, HH; Tsai, YHS; Zhao, JY; Zhang, WJ; Liu, QT; Meng, SS; Wang, Y; Wang, ZF
联系作者: Wang, ZF (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, Key Lab Computat Biol, Shanghai 200031, Peoples R China.
英文联系作者: Wang, ZF (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, Key Lab Computat Biol, Shanghai 200031, Peoples R China.
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发表年度: 2016
卷: 7
期:
页码: 11840
摘要: Aberrant splicing is frequently found in cancer, yet the biological consequences of such alterations are mostly undefined. Here we report that the Hippo-YAP signalling, a key pathway that regulates cell proliferation and organ size, is under control of a splicing switch. We show that TEAD4, the transcription factor that mediates Hippo-YAP signalling, undergoes alternative splicing facilitated by the tumour suppressor RBM4, producing a truncated isoform, TEAD4-S, which lacks an N-terminal DNA-binding domain, but maintains YAP interaction domain. TEAD4-S is located in both the nucleus and cytoplasm, acting as a dominant negative isoform to YAP activity. Consistently, TEAD4-S is reduced in cancer cells, and its re-expression suppresses cancer cell proliferation and migration, inhibiting tumour growth in xenograft mouse models. Furthermore, TEAD4-S is reduced in human cancers, and patients with elevated TEAD4-S levels have improved survival. Altogether, these data reveal a splicing switch that serves to fine tune the Hippo-YAP pathway.
英文摘要: Aberrant splicing is frequently found in cancer, yet the biological consequences of such alterations are mostly undefined. Here we report that the Hippo-YAP signalling, a key pathway that regulates cell proliferation and organ size, is under control of a splicing switch. We show that TEAD4, the transcription factor that mediates Hippo-YAP signalling, undergoes alternative splicing facilitated by the tumour suppressor RBM4, producing a truncated isoform, TEAD4-S, which lacks an N-terminal DNA-binding domain, but maintains YAP interaction domain. TEAD4-S is located in both the nucleus and cytoplasm, acting as a dominant negative isoform to YAP activity. Consistently, TEAD4-S is reduced in cancer cells, and its re-expression suppresses cancer cell proliferation and migration, inhibiting tumour growth in xenograft mouse models. Furthermore, TEAD4-S is reduced in human cancers, and patients with elevated TEAD4-S levels have improved survival. Altogether, these data reveal a splicing switch that serves to fine tune the Hippo-YAP pathway.
刊物名称: NATURE COMMUNICATIONS
英文刊物名称: NATURE COMMUNICATIONS
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学科: Multidisciplinary Sciences
英文学科: Multidisciplinary Sciences
影响因子: 12.124
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论文类别: Article
英文论文类别: Article
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