YAP enhances autophagic flux to promote breast cancer cell survival in response to nutrient deprivation.

YAP enhances autophagic flux to promote breast cancer cell survival in response to nutrient deprivation.
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YAP 增强自噬通量以促进乳腺癌细胞在营养缺乏时的存活

DOI:
10.1371/journal.pone.0120790
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Meng S
Meng S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Song Q;Mao B;Cheng J;Gao Y;Jiang K;Chen J;Yuan Z;Meng S

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Yes相关蛋白(雅普)是一种由Hippo肿瘤抑制通路失活的转录共激活因子,在多种癌症中作为癌蛋白发挥作用。然而,它对乳腺癌的贡献仍然存在争议。本研究探讨了雅普在营养剥夺(ND)条件下乳腺癌细胞中的作用。在这里,我们表明,雅普敲低敏感MCF 7乳腺癌细胞营养缺乏诱导的凋亡。此外,响应于ND,雅普增加自溶酶体降解,从而增强乳腺癌细胞中的细胞自噬通量。值得注意的是,自噬对于雅普在ND条件下保护MCF 7细胞免于凋亡至关重要。此外,TEA结构域(TEAD)家族的生长促进转录因子是必不可少的YAP介导的自噬调控。总的来说,我们的数据揭示了雅普在ND应激下促进乳腺癌细胞存活的作用,并揭示了雅普/TEAD在自噬调节中未被重视的功能。
The Yes-associated protein (YAP), a transcriptional coactivator inactivated by the Hippo tumor suppressor pathway, functions as an oncoprotein in a variety of cancers. However, its contribution to breast cancer remains controversial. This study investigated the role of YAP in breast cancer cells under nutrient deprivation (ND). Here, we show that YAP knockdown sensitized MCF7 breast cancer cells to nutrient deprivation-induced apoptosis. Furthermore, in response to ND, YAP increased the autolysosome degradation, thereby enhancing the cellular autophagic flux in breast cancer cells. Of note, autophagy is crucial for YAP to protect MCF7 cells from apoptosis under ND conditions. In addition, the TEA domain (TEAD) family of growth-promoting transcription factors was indispensable for YAP-mediated regulation of autophagy. Collectively, our data reveal a role for YAP in promoting breast cancer cell survival upon ND stress and uncover an unappreciated function of YAP/TEAD in the regulation of autophagy.
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