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| Status |
Public on Jan 23, 2017 |
| Title |
Cell fate and adhesion dynamics rely on Ror2-mediated alternative Wnt signaling during tumor progression |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Cellular heterogeneity in breast cancer encompasses many features, yet an understanding of the coexistence and regulation of various tumor cell subpopulations remains a significant challenge in cancer biology. In the current study, we approached tumor cell heterogeneity from the perspective of Wnt pathway biology to address how different modes of Wnt signaling shape the behaviors of diverse cell populations within a heterogeneous tumor landscape. Using a syngeneic TP53 null mouse model of breast cancer, we identified distinctions in the topology of canonical Wnt b-catenin dependent signaling activity and noncanonical b-catenin independent Ror2-mediated Wnt signaling across subtypes and within tumor cell subpopulations in vivo. We further discovered an antagonistic role for Ror2 in regulating canonical Wnt/b-catenin activity in vivo, where lentiviral shRNA depletion of Ror2 expression augmented canonical Wnt/b-catenin signaling activity across multiple basal-like models. Depletion of Ror2 expression yielded distinct phenotypic outcomes and divergent alterations in gene expression programs among different tumors, despite all sharing basal-like features. Notably, we uncovered cell state plasticity and adhesion dynamics regulated by Ror2, where Ras Homology Family Member A (RhoA) and Rho-Associated Coiled-Coil Kinase 1 (ROCK1) activity downstream of Dishevelled-2 (Dvl2) were implicated. Collectively, these studies illustrate the integration and collaboration of Wnt pathways in basal-like breast cancer, where Ror2 provides a spatiotemporal function to regulate the balance of Wnt signaling and cellular heterogeneity during tumor progression.
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| Overall design |
Total RNA from murine p53null mammary tumors was hybridized to agilent microarrays for gene expression analysis
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| Contributor(s) |
Roarty K, Pfefferle AD, Creighton CJ, Perou CM, Rosen JM |
| Citation missing |
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| Submission date |
Jan 18, 2017 |
| Last update date |
Jan 25, 2017 |
| Contact name |
Jeffrey Rosen |
| E-mail(s) |
jrosen@bcm.edu
|
| Organization name |
Baylor College of Medicine
|
| Department |
Department of Molecular and Cellular Biology
|
| Street address |
One Baylor Plaza M638
|
| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
77030 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL11383 |
Agi-perou-lab-custom-MM-144K-arrays-BARCODE25503 |
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| Samples (26)
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| Relations |
| BioProject |
PRJNA362571 |
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