Molecular Mechanisms Associated with ROR1-Mediated Drug Resistance: Crosstalk with Hippo-YAP/TAZ and BMI-1 Pathways
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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/8/812 |
| _version_ | 1797709850395803648 |
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| author | Hanna Karvonen Harlan Barker Laura Kaleva Wilhelmiina Niininen Daniela Ungureanu |
| author_facet | Hanna Karvonen Harlan Barker Laura Kaleva Wilhelmiina Niininen Daniela Ungureanu |
| author_sort | Hanna Karvonen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T06:42:49Z |
| format | Article |
| id | doaj.art-fe778c0fea734881ad89d78a75f9ade8 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T06:42:49Z |
| publishDate | 2019-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-fe778c0fea734881ad89d78a75f9ade82023-09-03T00:54:33ZengMDPI AGCells2073-44092019-08-018881210.3390/cells8080812cells8080812Molecular Mechanisms Associated with ROR1-Mediated Drug Resistance: Crosstalk with Hippo-YAP/TAZ and BMI-1 PathwaysHanna Karvonen0Harlan Barker1Laura Kaleva2Wilhelmiina Niininen3Daniela Ungureanu4Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, FinlandFaculty of Medicine and Health Technology, Tampere University, 33014 Tampere, FinlandFaculty of Medicine and Health Technology, Tampere University, 33014 Tampere, FinlandFaculty of Medicine and Health Technology, Tampere University, 33014 Tampere, FinlandFaculty of Medicine and Health Technology, Tampere University, 33014 Tampere, FinlandSignaling 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.https://www.mdpi.com/2073-4409/8/8/812Wnt signalingROR1Wnt5aHippo-YAP/TAZBMI-1drug resistancecancer stem cellsstemness |
| spellingShingle | Hanna Karvonen Harlan Barker Laura Kaleva Wilhelmiina Niininen Daniela Ungureanu Molecular Mechanisms Associated with ROR1-Mediated Drug Resistance: Crosstalk with Hippo-YAP/TAZ and BMI-1 Pathways Cells Wnt signaling ROR1 Wnt5a Hippo-YAP/TAZ BMI-1 drug resistance cancer stem cells stemness |
| title | Molecular Mechanisms Associated with ROR1-Mediated Drug Resistance: Crosstalk with Hippo-YAP/TAZ and BMI-1 Pathways |
| title_full | Molecular Mechanisms Associated with ROR1-Mediated Drug Resistance: Crosstalk with Hippo-YAP/TAZ and BMI-1 Pathways |
| title_fullStr | Molecular Mechanisms Associated with ROR1-Mediated Drug Resistance: Crosstalk with Hippo-YAP/TAZ and BMI-1 Pathways |
| title_full_unstemmed | Molecular Mechanisms Associated with ROR1-Mediated Drug Resistance: Crosstalk with Hippo-YAP/TAZ and BMI-1 Pathways |
| title_short | Molecular Mechanisms Associated with ROR1-Mediated Drug Resistance: Crosstalk with Hippo-YAP/TAZ and BMI-1 Pathways |
| title_sort | molecular mechanisms associated with ror1 mediated drug resistance crosstalk with hippo yap taz and bmi 1 pathways |
| topic | Wnt signaling ROR1 Wnt5a Hippo-YAP/TAZ BMI-1 drug resistance cancer stem cells stemness |
| url | https://www.mdpi.com/2073-4409/8/8/812 |
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