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论文题目: Loss of Scribble Promotes Snail Translation through Translocation of HuR and Enhances Cancer Drug Resistance
英文论文题目: Loss of Scribble Promotes Snail Translation through Translocation of HuR and Enhances Cancer Drug Resistance
第一作者: Zhou, Y; Chang, RX; Ji, WW; Wang, N; Qi, MY; Xu, Y; Guo, JY; Zhan, LX
英文第一作者: Zhou, Y; Chang, RX; Ji, WW; Wang, N; Qi, MY; Xu, Y; Guo, JY; Zhan, LX
联系作者: Zhan, LX (reprint author), 320 Yue Yang Rd, Shanghai 200031, Peoples R China.
英文联系作者: Zhan, LX (reprint author), 320 Yue Yang Rd, Shanghai 200031, Peoples R China.
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发表年度: 2016
卷: 291
期: 1
页码: 291-302
摘要: Drug resistance of cancer cells to various therapeutic agents and molecular targets is a major problem facing current cancer research. The tumor suppressor gene Scribble encodes a polarity protein that is conserved between Drosophila and mammals; loss of the locus disrupts cell polarity, inhibits apoptosis, and mediates cancer process. However, the role of Scribble in drug resistance remains unknown. We show here that knockdown of Scribble enhances drug resistance by permitting accumulation of Snail, which functions as a transcription factor during the epithelial-mesenchymal transition. Then, loss of Scribble activates the mRNA-binding protein human antigen R (HuR) by facilitating translocation of HuR from the nucleus to the cytoplasm. Furthermore, we demonstrate HuR can recognize AU-rich elements of the Snail-encoding mRNA, thereby regulating Snail translation. Moreover, loss of Scribble-induced HuR translocation mediates the accumulation of Snail via activation of the p38 MAPK pathway. Thus, this work clarifies the role of polarity protein Scribble, which is directly implicated in the regulation of developmental transcription factor Snail, and suggesting a mechanism for Scribble mediating cancer drug resistance.
英文摘要: Drug resistance of cancer cells to various therapeutic agents and molecular targets is a major problem facing current cancer research. The tumor suppressor gene Scribble encodes a polarity protein that is conserved between Drosophila and mammals; loss of the locus disrupts cell polarity, inhibits apoptosis, and mediates cancer process. However, the role of Scribble in drug resistance remains unknown. We show here that knockdown of Scribble enhances drug resistance by permitting accumulation of Snail, which functions as a transcription factor during the epithelial-mesenchymal transition. Then, loss of Scribble activates the mRNA-binding protein human antigen R (HuR) by facilitating translocation of HuR from the nucleus to the cytoplasm. Furthermore, we demonstrate HuR can recognize AU-rich elements of the Snail-encoding mRNA, thereby regulating Snail translation. Moreover, loss of Scribble-induced HuR translocation mediates the accumulation of Snail via activation of the p38 MAPK pathway. Thus, this work clarifies the role of polarity protein Scribble, which is directly implicated in the regulation of developmental transcription factor Snail, and suggesting a mechanism for Scribble mediating cancer drug resistance.
刊物名称: JOURNAL OF BIOLOGICAL CHEMISTRY
英文刊物名称: JOURNAL OF BIOLOGICAL CHEMISTRY
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学科: Biochemistry & Molecular Biology
英文学科: Biochemistry & Molecular Biology
影响因子: 4.125
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论文类别: Article
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