Activation of Aurora A kinase increases YAP stability via blockage of autophagy

Cell Death Dis. 2019 Jun 3;10(6):432. doi: 10.1038/s41419-019-1664-4.

Abstract

Transcription cofactor Yes-associated protein (YAP) plays an important role in cancer progression. Here, we found that Aurora A kinase expression was positively correlated with YAP in lung cancer. Aurora A depletion suppresses lung cancer cell colony formation, which could be reversed by YAP ectopic overexpression. In addition, activation of Aurora A increases YAP protein abundance through maintaining its protein stability. Consistently, the transcriptional activity of YAP is increased upon Aurora A activation. We further showed that shAURKA suppressed YAP expression in the absence of Lats1/2, indicating that Aurora A regulates YAP independently of Hippo pathway. Instead, Aurora A induced blockage of autophagy to up-regulate YAP expression. Collectively, our findings provide insights into regulatory mechanisms of YAP expression in lung cancer development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Aurora Kinase A / genetics
  • Aurora Kinase A / metabolism*
  • Autophagy* / genetics
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Hippo Signaling Pathway
  • Humans
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Stability
  • Signal Transduction / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • LATS1 protein, human
  • AURKA protein, human
  • Aurora Kinase A
  • Protein Serine-Threonine Kinases
  • Proteasome Endopeptidase Complex