From TGFb signalling in cancer to the molecular landscape of cutaneous squamous cell carcinoma

Abstract

The Transforming Growth Factor b superfamily of cytokines has diverse and pleiotropic roles during development, tissue homeostasis and disease pathogenesis. These factors can regulate all of the hallmarks of cancer acting to both inhibit and promote cancer progression in a context dependent manner. The Inman lab seeks to identify when and how TGFb acts as a tumour suppressor or a tumour promoter and is investigating TGFb signalling in the development and metastatic spread of squamous cell carcinomas (SCC), melanoma, breast cancer, glioblastoma, pancreatic and colon cancer. Current work focuses on identifying critical cellular targets and mediators of TGFb signalling using gene expression profiling, proteomics, genomics and in-vivo approaches. I will discuss our current efforts to understand the role of novel TGFb target genes in breast cancer cell migration, invasion and clonogenicity coupled with how TGFb signalling contributes to BRAF mutant melanoma, cSCC and HNSCC progression. Given our findings that TGFb signalling is intimately involved in cSCC development we have now joined an international consortium to study the molecular landscape of this disease. I will reveal how the analysis of whole exome sequencing of primary cSCC tumours is yielding new insight into the mutagens, genes, signalling pathways and processes that drive cSCC.