Targeting Oncogenic Wnt/β-Catenin Signaling in Adrenocortical Carcinoma Disrupts ECM Expression and Impairs Tumor Growth
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Transcriptome Data Analysis
2.2. Cell Culture and In Vitro Compounds
2.3. Assessment of Cell Viability
2.4. qRT–PCR
2.5. Western Blots
2.6. Generation of Luciferase-Expressing Cell Lines
2.7. Animals and Animal Care
2.8. Xenograft Model of ACC
2.9. Histopathology and Immunochemistry
2.10. Statistics
3. Results
3.1. A Wnt/β-Catenin-Driven Gene Signature Is Associated with Poor Patient Outcomes in ACC
3.2. Wnt/β-Catenin Activity Is Associated with ECM Expression in ACC
3.3. Inhibition of Wnt/β-Catenin Reduces ACC Viability and Disrupts ECM Expression
3.4. An Orthotopic Xenograft Model of ACC Recapitulates High-Grade ACC with Metastatic Potential
3.5. Tegavivint Inhibits High-Grade ACC Growth In Vivo
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ACC | Adrenocortical carcinoma |
DFS | Disease-free survival |
ECM | Extracellular matrix |
FAP | Familial Adenomatous Polyposis |
GSEA | Gene set enrichment analysis |
GOF | Gain-of-function |
GSVA | Gene set variation analysis |
HPF | High-power fields |
ICA | Independent Component Analysis |
OS | Overall Survival |
LOF | Loss-of-function |
SD | Standard Deviation |
TCGA | The Cancer Genome Atlas Project |
TMA | Tissue Microarray |
References
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Cell Line | Cell Number | Average Time to Detection (SD) | Average Time to Endpoint (SD) | Tumor Engrafment | Liver Metastasis | Lung Metastasis |
---|---|---|---|---|---|---|
Y1 | 2 × 105 | 2.5 weeks (0.9) | 5.1 weeks (1.0) | 89% | 50% | 83% |
NCI-H295R | 2 × 105 | 3.6 weeks (0.9) | 8.9 weeks (3.0) | 80% | 0% | 0% |
1 × 106 | 3.4 weeks (0.7) | 6.9 weeks (2.7) | 100% | 13% | 0% |
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Penny, M.K.; Lerario, A.M.; Basham, K.J.; Chukkapalli, S.; Mohan, D.R.; LaPensee, C.; Converso-Baran, K.; Hoenerhoff, M.J.; Suárez-Fernández, L.; Rey, C.G.d.; et al. Targeting Oncogenic Wnt/β-Catenin Signaling in Adrenocortical Carcinoma Disrupts ECM Expression and Impairs Tumor Growth. Cancers 2023, 15, 3559. https://doi.org/10.3390/cancers15143559
Penny MK, Lerario AM, Basham KJ, Chukkapalli S, Mohan DR, LaPensee C, Converso-Baran K, Hoenerhoff MJ, Suárez-Fernández L, Rey CGd, et al. Targeting Oncogenic Wnt/β-Catenin Signaling in Adrenocortical Carcinoma Disrupts ECM Expression and Impairs Tumor Growth. Cancers. 2023; 15(14):3559. https://doi.org/10.3390/cancers15143559
Chicago/Turabian StylePenny, Morgan K., Antonio M. Lerario, Kaitlin J. Basham, Sahiti Chukkapalli, Dipika R. Mohan, Chris LaPensee, Kimber Converso-Baran, Mark J. Hoenerhoff, Laura Suárez-Fernández, Carmen González del Rey, and et al. 2023. "Targeting Oncogenic Wnt/β-Catenin Signaling in Adrenocortical Carcinoma Disrupts ECM Expression and Impairs Tumor Growth" Cancers 15, no. 14: 3559. https://doi.org/10.3390/cancers15143559
APA StylePenny, M. K., Lerario, A. M., Basham, K. J., Chukkapalli, S., Mohan, D. R., LaPensee, C., Converso-Baran, K., Hoenerhoff, M. J., Suárez-Fernández, L., Rey, C. G. d., Giordano, T. J., Han, R., Newman, E. A., & Hammer, G. D. (2023). Targeting Oncogenic Wnt/β-Catenin Signaling in Adrenocortical Carcinoma Disrupts ECM Expression and Impairs Tumor Growth. Cancers, 15(14), 3559. https://doi.org/10.3390/cancers15143559