Academic Bibliography

 Search 200 years of publications by Ghent University researchers.
Advanced search
1 file | 14.37 MB
Add to list
  1. Search results
  2. Dual targeting of MAPK and PI3K pathw...

Dual targeting of MAPK and PI3K pathways unlocks redifferentiation of Braf-mutated thyroid cancer organoids

Helene Lasolle, Andrea Schiavo, Adrien Tourneur, Pierre Gillotay, Barbara de Faria da Fonseca, Lucieli Ceolin, Olivier Monestier, Benilda Aganahi, Laura Chomette, Marina Malta Letro Kizys, et al.
(2024) ONCOGENE. 43(3). p.155-170
Author
Organization
Abstract
Thyroid cancer is the most common endocrine malignancy and several genetic events have been described to promote the development of thyroid carcinogenesis. Besides the effects of specific mutations on thyroid cancer development, the molecular mechanisms controlling tumorigenesis, tumor behavior, and drug resistance are still largely unknown. Cancer organoids have been proposed as a powerful tool to study aspects related to tumor development and progression and appear promising to test individual responses to therapies. Here, using mESC-derived thyroid organoids, we developed a Braf(V637E)-inducible model able to recapitulate the features of papillary thyroid cancer in vitro. Overexpression of the murine Braf(V637E) mutation, equivalent to Braf(V600E) in humans, rapidly triggers to MAPK activation, cell dedifferentiation, and disruption of follicular organization. Braf(V637E)-expressing organoids show a transcriptomic signature for p53, focal adhesion, ECM-receptor interactions, EMT, and inflammatory signaling pathways. Finally, PTC-like thyroid organoids were used for drug screening assays. The combination of MAPK and PI3K inhibitors reversed Braf(V637E) oncogene-promoted cell dedifferentiation while restoring thyroid follicle organization and function in vitro. Our results demonstrate that pluripotent stem cells-derived thyroid cancer organoids can mimic tumor development and features while providing an efficient tool for testing novel targeted therapies.

Downloads

  • Download
    published version.pdf
    • full text (Published version)
    • |
    • open access
    • |
    • PDF
    • |
    • 14.37 MB

Citation

Please use this url to cite or link to this publication:

MLA
Lasolle, Helene, et al. “Dual Targeting of MAPK and PI3K Pathways Unlocks Redifferentiation of Braf-Mutated Thyroid Cancer Organoids.” ONCOGENE, vol. 43, no. 3, 2024, pp. 155–70, doi:10.1038/s41388-023-02889-y.
APA
Lasolle, H., Schiavo, A., Tourneur, A., Gillotay, P., de Faria da Fonseca, B., Ceolin, L., … Romitti, M. (2024). Dual targeting of MAPK and PI3K pathways unlocks redifferentiation of Braf-mutated thyroid cancer organoids. ONCOGENE, 43(3), 155–170. https://doi.org/10.1038/s41388-023-02889-y
Chicago author-date
Lasolle, Helene, Andrea Schiavo, Adrien Tourneur, Pierre Gillotay, Barbara de Faria da Fonseca, Lucieli Ceolin, Olivier Monestier, et al. 2024. “Dual Targeting of MAPK and PI3K Pathways Unlocks Redifferentiation of Braf-Mutated Thyroid Cancer Organoids.” ONCOGENE 43 (3): 155–70. https://doi.org/10.1038/s41388-023-02889-y.
Chicago author-date (all authors)
Lasolle, Helene, Andrea Schiavo, Adrien Tourneur, Pierre Gillotay, Barbara de Faria da Fonseca, Lucieli Ceolin, Olivier Monestier, Benilda Aganahi, Laura Chomette, Marina Malta Letro Kizys, Lieven Haenebalcke, Tim Pieters, Steven Goossens, Jody Haigh, Vincent Detours, Ana Luiza Silva Maia, Sabine Costagliola, and Mirian Romitti. 2024. “Dual Targeting of MAPK and PI3K Pathways Unlocks Redifferentiation of Braf-Mutated Thyroid Cancer Organoids.” ONCOGENE 43 (3): 155–170. doi:10.1038/s41388-023-02889-y.
Vancouver
1.
Lasolle H, Schiavo A, Tourneur A, Gillotay P, de Faria da Fonseca B, Ceolin L, et al. Dual targeting of MAPK and PI3K pathways unlocks redifferentiation of Braf-mutated thyroid cancer organoids. ONCOGENE. 2024;43(3):155–70.
IEEE
[1]
H. Lasolle et al., “Dual targeting of MAPK and PI3K pathways unlocks redifferentiation of Braf-mutated thyroid cancer organoids,” ONCOGENE, vol. 43, no. 3, pp. 155–170, 2024.
@article{01HRVW2DB5YSZ07TWCHFHEY21E,
  abstract     = {{Thyroid cancer is the most common endocrine malignancy and several genetic events have been described to promote the development of thyroid carcinogenesis. Besides the effects of specific mutations on thyroid cancer development, the molecular mechanisms controlling tumorigenesis, tumor behavior, and drug resistance are still largely unknown. Cancer organoids have been proposed as a powerful tool to study aspects related to tumor development and progression and appear promising to test individual responses to therapies. Here, using mESC-derived thyroid organoids, we developed a Braf(V637E)-inducible model able to recapitulate the features of papillary thyroid cancer in vitro. Overexpression of the murine Braf(V637E) mutation, equivalent to Braf(V600E) in humans, rapidly triggers to MAPK activation, cell dedifferentiation, and disruption of follicular organization. Braf(V637E)-expressing organoids show a transcriptomic signature for p53, focal adhesion, ECM-receptor interactions, EMT, and inflammatory signaling pathways. Finally, PTC-like thyroid organoids were used for drug screening assays. The combination of MAPK and PI3K inhibitors reversed Braf(V637E) oncogene-promoted cell dedifferentiation while restoring thyroid follicle organization and function in vitro. Our results demonstrate that pluripotent stem cells-derived thyroid cancer organoids can mimic tumor development and features while providing an efficient tool for testing novel targeted therapies.}},
  author       = {{Lasolle, Helene and  Schiavo, Andrea and  Tourneur, Adrien and  Gillotay, Pierre and  de Faria da Fonseca, Barbara and  Ceolin, Lucieli and  Monestier, Olivier and  Aganahi, Benilda and  Chomette, Laura and  Kizys, Marina Malta Letro and Haenebalcke, Lieven and Pieters, Tim and Goossens, Steven and  Haigh, Jody and  Detours, Vincent and  Maia, Ana Luiza Silva and  Costagliola, Sabine and  Romitti, Mirian}},
  issn         = {{0950-9232}},
  journal      = {{ONCOGENE}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{155--170}},
  title        = {{Dual targeting of MAPK and PI3K pathways unlocks redifferentiation of Braf-mutated thyroid cancer organoids}},
  url          = {{http://doi.org/10.1038/s41388-023-02889-y}},
  volume       = {{43}},
  year         = {{2024}},
}
Altmetric
View in Altmetric
Web of Science
Times cited: