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AMOTL1 Promotes Breast Cancer Progression and Is Antagonized by Merlin

Christophe Couderc1, Alizée Boin1, Laetitia Fuhrmann2

  • 1Institut Curie, Paris, France; CNRS UMR144, Paris, France.

Neoplasia (New York, N.Y.)
|January 26, 2016
PubMed

Insights

The Hippo signaling pathway regulates breast cancer aggressiveness via AMOTL1. Merlin loss and YAP activation increase AMOTL1, promoting tumor cell migration and proliferation, and predicting relapse risk.

Area of Science:

  • Cell Biology
  • Oncology
  • Molecular Biology

Background:

  • The Hippo signaling pathway is crucial for cell fate regulation.
  • Its role in cancer extends beyond YAP transcriptional activity and MST/LATS kinase regulation.

Purpose of the Study:

  • Investigate the role of AMOTL1 as a Hippo signaling effector in breast cancer.
  • Elucidate the mechanisms linking Hippo signaling, AMOTL1, and tumor aggressiveness.

Main Methods:

  • Investigated canonical and noncanonical Hippo signaling modulation of AMOTL1 levels.
  • Examined Merlin's role in AMOTL1 proteasomal degradation via NEDD ubiquitin ligases.
  • Assessed YAP's effect on AMOTL1 expression.
  • Analyzed AMOTL1 protein levels in human breast tumors and lymph node metastasis.

Main Results:

  • AMOTL1 connects Hippo signaling to breast cancer cell aggressiveness.
  • Merlin directly interacts with AMOTL1, promoting its degradation; YAP stimulates AMOTL1 expression.
  • Loss of Merlin and YAP activation lead to elevated AMOTL1 levels in breast cancers.
  • AMOTL1 expression drives tumor cell migration and proliferation via c-Src activation.
  • AMOTL1 protein is upregulated during cancer progression and predicts relapse risk in lymph node metastasis.

Conclusions:

  • Hippo signaling promotes breast cancer progression by modulating AMOTL1 expression.
  • AMOTL1 is a key mediator linking Hippo pathway dysregulation to tumor aggressiveness and metastatic potential.

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