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Molecular Mechanisms Associated with ROR1-Mediated Drug Resistance: Crosstalk with Hippo-YAP/TAZ and BMI-1 Pathways

1
Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland
2
Tays Cancer Center, Tampere University Hospital, 33520 Tampere, Finland
*
Author to whom correspondence should be addressed.
Cells 2019, 8(8), 812; https://doi.org/10.3390/cells8080812
Received: 11 July 2019 / Revised: 30 July 2019 / Accepted: 31 July 2019 / Published: 2 August 2019
(This article belongs to the Special Issue Wnt Signaling in Health and Diseases)
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Abstract

Signaling via the Wnt-related receptor tyrosine kinase-like orphan receptor 1 (ROR1) triggers tumorigenic features associated with cancer stem cells (CSCs) and epithelial–mesenchymal transition (EMT), while aberrant expression of ROR1 is strongly linked to advanced disease progression and chemoresistance. Several recent studies have shown that Wnt5a binding to ROR1 promotes oncogenic signaling by activating multiple pathways such as RhoA/Rac1 GTPases and PI3K/AKT, which in turn could induce transcriptional coactivator YAP/TAZ or polycomb complex protein BMI-1 signaling, respectively, to sustain stemness, metastasis and ultimately drug-resistance. These data point towards a new feedback loop during cancer development, linking Wnt5a-ROR1 signaling activation to YAP/TAZ or BMI-1 upregulation that could play an important role in disease progression and treatment resistance. This review focuses on the crosstalk between Wnt5a-ROR1 and YAP/TAZ or the BMI-1 signaling network, together with the current advancements in targeted strategies for ROR1-positive cancers. View Full-Text
Keywords: Wnt signaling; ROR1; Wnt5a; Hippo-YAP/TAZ; BMI-1; drug resistance; cancer stem cells; stemness Wnt signaling; ROR1; Wnt5a; Hippo-YAP/TAZ; BMI-1; drug resistance; cancer stem cells; stemness
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Karvonen, H.; Barker, H.; Kaleva, L.; Niininen, W.; Ungureanu, D. Molecular Mechanisms Associated with ROR1-Mediated Drug Resistance: Crosstalk with Hippo-YAP/TAZ and BMI-1 Pathways. Cells 2019, 8, 812.

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