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Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
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Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor

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Sox2 antagonizes the Hippo pathway to maintain stemness in cancer cells

Upal Basu-Roy1, N Sumru Bayin2, Kirk Rattanakorn1

  • 1Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA.

Nature Communications
|April 3, 2015
PubMed

Insights

Sox2 maintains osteosarcoma cancer stem cells by repressing the Hippo pathway, increasing YAP activity. Targeting YAP offers a potential therapy for Sox2-driven cancers like osteosarcomas and glioblastomas.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Stem Cell Biology

Background:

  • The Hippo pathway is a tumor suppressor that inhibits YAP, a growth-promoting coactivator.
  • Sox2 maintains cancer stem cells (CSCs) in osteosarcomas.

Purpose of the Study:

  • To investigate how Sox2 maintains CSCs in osteosarcomas.
  • To elucidate the interaction between Sox2, the Hippo pathway, and YAP in osteosarcoma.

Main Methods:

  • Analysis of Sox2, Hippo pathway components (Nf2, WWC1), and YAP expression in osteosarcoma CSCs and differentiated cells.
  • Assessment of YAP function and tumorigenicity upon YAP depletion in osteosarcomas.

Main Results:

  • Sox2 directly represses Hippo pathway activators Nf2 (Merlin) and WWC1 (Kibra) in osteosarcoma CSCs.
  • This repression leads to enhanced YAP activity, which is characteristic of the CSC fraction.
  • YAP depletion significantly reduces CSCs and osteosarcoma tumorigenicity.
  • The Sox2-Hippo-YAP axis is conserved in Sox2-dependent cancers like glioblastomas.

Conclusions:

  • Sox2 promotes osteosarcoma CSC maintenance by antagonizing the tumor-suppressive Hippo pathway, thereby increasing YAP function.
  • Targeting YAP transcriptional activity presents a potential therapeutic strategy for Sox2-dependent tumors.

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