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Autophagy promotes triple negative breast cancer metastasis via YAP nuclear localization

Wei Chen1, Yuxin Bai2, Chrishma Patel2

  • 1Department of Mechanical Engineering, McMaster University, Hamilton, ON, L8S 0A3, Canada.

Biochemical and Biophysical Research Communications
|October 9, 2019
PubMed

Insights

Triple-negative breast cancer (TNBC) metastasis is linked to autophagy and the YAP signaling pathway. Inhibiting YAP nuclear entry reduces TNBC cell invasion, suggesting YAP as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Triple-negative breast cancer (TNBC) is an aggressive subtype with unclear metastatic mechanisms.
  • Autophagy plays a critical role in TNBC progression.
  • The Hippo signaling pathway effector, YAP, is known to promote autophagy.

Purpose of the Study:

  • To investigate the regulation of autophagy by YAP signaling in TNBC metastasis.
  • To compare YAP signaling, autophagy, and invasiveness in TNBC versus ER-positive breast cancer cells.

Main Methods:

  • Profiling analysis of YAP signaling and subcellular localization.
  • Assessment of autophagosome formation and cell invasiveness.
  • Comparison of TNBC cell lines (MDA-MB-231, Hs 578T) with an ER-positive cell line (MCF7).

Main Results:

  • YAP expression was significantly upregulated in TNBC.
  • Autophagy induction led to YAP nuclear translocation and increased ANKRD1 expression in TNBC.
  • Inhibition of YAP nuclear entry reduced TNBC cell migration and invasion.

Conclusions:

  • Established the autophagy-YAP-metastasis axis in TNBC.
  • YAP nuclear entry is crucial for TNBC cell invasiveness.
  • Targeting YAP presents a potential therapeutic strategy for TNBC.
Keywords:
AutophagyAutophagy-YAP-Metastasis axisBreast cancerCancer metastasisTNBCYAP

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