Cytoskeleton and metastasis lab
Instituto de Investigaciones Biomédicas “Alberto Sols” CSIC-UAM (IIBM)
DESCRIPTION OF THE OFFER
Studying the regulation of Myosin II cytoskeleton during adaptation to targeted therapy in melanoma and how resistant cells are more vulnerable to Myosin II inhibition
Resistance to current therapies is a persistent problem in melanoma management. Melanoma cells seem to adapt to MAPK pathwaytargeted therapy through a proteomic and transcriptomic reprogramming directed to remodel the cytoskeleton and over-activate Myosin II. Actin-myosin cytoskeleton is essential for cell migration and invasion, among other cellular processes. This cytoskeletal remodelling leads to a higher sensitivity to inhibition of Myosin II activity in therapy-resistant cells, which can be exploited therapeutically. Therefore, Myosin II is not only essential for migration and invasion, but also for promoting survival of melanoma cells and, hence, therapy failure.
The main goal of this project is to investigate how Myosin II expression and activity are controlled during early adaptation to therapy.
Since later in resistant cells restored Myosin II activity becomes a vulnerability, we aim to understand which cellular and molecular alterations under Myosin II inhibition underlie this differential susceptibility.
Finally, we propose to study if targeting Myosin II may prevent or delay emergence of resistance to MAPK inhibitors.
Orgaz et al 2020 Cancer Cell 37(1):85-103.e9. doi: 10.1016/j.ccell.2019.12.003 (https://pubmed.ncbi.nlm.nih.gov/31935375/)
Orgaz and Sanz Moreno 2020 Mol Cell Oncol 7(3):1735911. doi: 10.1080/23723556.2020.1735911 (https://pubmed.ncbi.nlm.nih.gov/32391428/)
Biomolecules & Cell D.
Jose Luis Orgaz Bueno