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RUNX1 and RUNX3 protect against YAP-mediated EMT, stem-ness and shorter survival outcomes in breast cancer

Madhura Kulkarni1,2, Tuan Zea Tan1, Nurfarhanah Bte Syed Sulaiman1

  • 1Cancer Science Institute, NUS, Singapore.

Oncotarget
|March 28, 2018
PubMed

Insights

RUNX1 and RUNX3 suppress the oncogenic YAP protein in breast cancer. This interaction inhibits tumor progression and improves patient survival, offering a new prognostic tool for cancer recurrence.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The Hippo pathway effector, Yes-associated protein (YAP), is a key driver in solid tumor progression.
  • Understanding YAP's regulatory mechanisms is crucial for developing targeted breast cancer therapies.

Purpose of the Study:

  • To identify novel regulators of YAP's oncogenic function in breast cancer.
  • To investigate the interplay between YAP, RUNX1, and RUNX3 in breast cancer progression and patient survival.

Main Methods:

  • Investigated the interaction between RUNX proteins and YAP in mammary epithelial cell lines.
  • Analyzed whole-genome expression profiles of breast cancer samples.
  • Correlated YAP, RUNX1, and RUNX3 expression levels with patient survival outcomes and gene signatures (EMT, stemness).

Main Results:

  • RUNX1 and RUNX3 were identified as novel negative regulators of YAP's oncogenic activity.
  • RUNX1/RUNX3 expression abrogated YAP-mediated pro-tumorigenic properties, including migration and stemness.
  • High RUNX1/RUNX3 expression correlated with better patient survival and reduced enrichment of EMT and stemness signatures, even with high YAP levels.

Conclusions:

  • RUNX1 and RUNX3 antagonize YAP's oncogenic function in breast cancer, providing mechanistic insight into oncogene-tumor suppressor interplay.
  • The YAP-RUNX1/RUNX3 interaction represents a potential prognostic tool for predicting breast cancer recurrence.
Keywords:
EMTRUNX1 and RUNX3YAPbreast cancerstem-ness

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