Date: Monday 26 February, 12.00pmVenue: Garrod Building 2.48 and Online | Join the meetingMeeting ID: 382 199 485 623 | Passcode: URVd92Speaker: Dr Priyanka Bhosale (King’s College London)Title: Cancer associated mutations lead to altered differentiation and mitochondrial dynamics in oral SCCHost: Dr Ines Sequeira
Oral squamous cell carcinoma (OSCC) is a highly heterogenous disease. This heterogeneity is attributed to selection and clonal expansion of the tumour initiating cells that acquires various molecular and genetic alterations leading to a diverse oncogenomic landscape. Studies have identified frequent mutations in TP53, FAT1, CASP8, and NOTCH1 gene locus in majority of OSCC cases. The type of mutation, the stage at which they occur during tumour progression, and their impact on both the epithelium and/or the immune microenvironment are major determinants of tumour behaviour and patient outcomes. Using different model systems, we look at the biological impact of these mutations in OSCC. FAT1 is a transmembrane cadherin that plays a crucial role in regulation of Hippo and Wnt signalling pathways and it is known to be a tumour-suppressor in a few cancer types while oncogenic in others. Here, by using different epithelial specific mutations of FAT1, we show the effect of FAT1 on metabolic rewiring of epithelial cells to hijack the differentiation process which ultimately determines OSCC phenotype and the tumor development trajectories. Overall, our comprehensive analysis of location specific FAT1 mutations gives a possible mechanism by which FAT1 can either promote or supress cancer growth in a context dependent manner.