TACAN regulates mesenchymal versus amoeboid cell states in glioblastoma
Aperçu du projet
Glioblastoma Multiforme (GBM) is the most common and aggressive brain tumour in adults. Current treatment includes surgical resection, chemotherapy, and radiation. However, since GBM is fastgrowing and highly invasive, existing therapies often result in tumour recurrence and poor survival outcomes, emphasizing the importance of the development of novel therapeutic targets. During tumour invasion, tumour cells encounter diverse tissue environments and the ability of tumour cells to adapt their cell state is advantageous for tumour progression. I study how changes in tumour cell states influence GBM growth and invasion into healthy tissue and determine regulators of the transition between amoeboid (rounded) and mesenchymal (elongated) cell states. Existing GBM patient data revealed that the expression levels of TACAN, a putative fatty acid elongase, is correlated with poor patient survival. Furthermore, I found that genetic knockdown of TACAN promotes a switch in cell states from mesenchymal to amoeboid. Based on these findings I hypothesize that TACAN promotes amoeboid to mesenchymal cell state transition in GBM by regulating plasma membrane lipid composition, thus promoting GBM invasion. In this project, I will characterize the role of amoeboid and mesenchymal cell states in GBM progression and elucidate the role of TACAN as a putative fatty acid elongase and a regulator of mesenchymal cell state in GBM. Ultimately, I will uncover new therapeutic targets to combat this recurring and devastating disease.
Chef d'équipe
Zaleena Akheralie , University of Toronto
Partenaire et Donateurs
Henry and Berenice Kaufmann Foundation