Poster Presentation 40th Annual Lorne Genome Conference 2019

The Role of Planar Cell Polarity in the Initiation of Prostate Cancer (#150)

Andrew W Farrell 1 , Patrick Humbert 1
  1. La Trobe University, Bundoora, VICTORIA, Australia

Prostate Cancer (PrCa) constitutes a major health issue and is the second most common cause of male cancer related deaths in Australia. However, despite its prevalence, a detailed molecular understanding of prostate carcinogenesis is lacking and the discovery of novel therapeutics and biomarkers for PrCa is sorely needed. Planar cell polarity (PCP) refers to the coordinated alignment of cell polarity across the tissue plane, and is key to communication between neighbouring cells.  PCP has also been shown to mediate many key cellular events such as cell proliferation, apoptosis and migration, thus, it is not surprising that mutations of key PCP genes have been implicated in driving many human cancers, such as prostate cancer.

In order to better understand the effects of PCP on PrCa, genetically engineered mouse models harbouring mutations of the PCP genes Celsr1, Ptk7 and Vangl2 were utilized. It was discovered that mice harbouring PCP mutations were predisposed to prostate neoplasia. Further, using 3D culture of prostate cells in matrigel, mutant PCP cells showed increased prostate organoid formation. These experiments suggest that the PCP pathway exerts a tumour suppressive role within the prostate, and further experiments to understand the key downstream effectors of PCP signaling in the prostate may provide novel therapeutic targets for PrCa in the future.