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De Novo Generation of Somatic Stem Cells by YAP/TAZ
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Molecular Mechanisms Associated with ROR1-Mediated Drug Resistance: Crosstalk with Hippo-YAP/TAZ and BMI-1 Pathways

Hanna Karvonen1,2, Harlan Barker1, Laura Kaleva1,2

  • 1Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland.

Cells
|August 7, 2019
PubMed

Insights

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) signaling drives cancer stemness and metastasis. Targeting the Wnt5a-ROR1 pathway may overcome drug resistance in ROR1-positive cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling

Background:

  • Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is implicated in cancer stem cell (CSC) and epithelial-mesenchymal transition (EMT) phenotypes.
  • Aberrant ROR1 expression correlates with advanced disease, metastasis, and chemoresistance.
  • Wnt5a binding to ROR1 activates oncogenic pathways, including RhoA/Rac1 and PI3K/AKT.

Purpose of the Study:

  • To review the crosstalk between Wnt5a-ROR1 signaling and YAP/TAZ or BMI-1 networks in cancer.
  • To discuss current targeted strategies for ROR1-positive cancers.

Main Methods:

  • Literature review of studies on ROR1, Wnt5a, YAP/TAZ, BMI-1, CSCs, EMT, and targeted therapies.
  • Analysis of signaling pathways involved in ROR1-mediated oncogenesis.

Main Results:

  • Wnt5a-ROR1 signaling activates RhoA/Rac1 and PI3K/AKT pathways.
  • These pathways can lead to the upregulation of YAP/TAZ or BMI-1, promoting stemness and metastasis.
  • A feedback loop exists between Wnt5a-ROR1 and YAP/TAZ or BMI-1 signaling in cancer development.

Conclusions:

  • The Wnt5a-ROR1 pathway, in conjunction with YAP/TAZ or BMI-1, plays a critical role in cancer progression and treatment resistance.
  • Targeting ROR1 offers a promising therapeutic strategy for ROR1-positive cancers.
Keywords:
BMI-1Hippo-YAP/TAZROR1Wnt signalingWnt5acancer stem cellsdrug resistancestemness

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