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

Qinghe Song; Beibei Mao; Jinbo Cheng; Yuhao Gao; Ke Jiang; Jun Chen; Zengqiang Yuan; Songshu Meng

doi:10.1371/journal.pone.0120790

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

PLoS One. 2015 Mar 26;10(3):e0120790. doi: 10.1371/journal.pone.0120790. eCollection 2015.

Authors

Qinghe Song¹, Beibei Mao², Jinbo Cheng², Yuhao Gao¹, Ke Jiang³, Jun Chen⁴, Zengqiang Yuan¹, Songshu Meng³

Affiliations

¹ State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
² State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
³ Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, Dalian, Liaoning, China.
⁴ Center of Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, China.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism*
Apoptosis / genetics
Autophagy / genetics
Breast Neoplasms / genetics
Breast Neoplasms / metabolism*
Cell Line, Tumor
Cell Survival / genetics
Female
Gene Knockdown Techniques
Humans
Lysosomes / metabolism
MCF-7 Cells
Phosphoproteins / genetics
Phosphoproteins / metabolism*
Protein Binding
Transcription Factors / metabolism
YAP-Signaling Proteins

Substances

Adaptor Proteins, Signal Transducing
Phosphoproteins
Transcription Factors
YAP-Signaling Proteins
YAP1 protein, human

Grants and funding

This work was supported by the Ministry of Science and Technology of China (973-2012CB910701 to ZY; http://www.most.gov.cn/eng/); and the National Science Foundation of China (81125010 and 81030025 to ZY, 81372471 to SM; http://www.nsfc.gov.cn/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.