Poster Presentation 25th Lorne Cancer Conference 2013

The asymmetric cell division regulator GPSM2 controls mammary progenitor activity and breast cancer progression. (#188)

Nathan J Godde 1 , Lorey K Smith 1 , Samantha J Williams 1 , Patrick O Humbert 1
  1. Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia

Stem and progenitor cells polarise and divide asymmetrically to regulate cell diversification during tissue development. Tight control of this process is essential during normal tissue morphogenesis and involves cell polarity mechanisms to segregate cell fate determinants and to reorientate the mitotic spindle appropriately. Loss of polarity is a hallmark of cancer and it has been suggested that impairment of asymmetric cell divisions could result in the inappropriate outgrowth of uncommitted cells leading to tumour formation. GPSM2 is a polarity protein which acts as a key component of the asymmetric division machinery. GPSM2 coordinates spindle orientation and segregation of cell fate determinants during asymmetric divisions of Drosophila progenitors and mutant Drosophila neuroblasts lacking GPSM2 have been shown to form tumours when transplanted into adult hosts. Whilst these Drosophila studies have supported a role for defective asymmetric cell divisions in tumour formation, further evidence in mammalian models of cancer has been lacking. We have recently identified GPSM2 in a polarity tumour suppressor screen and shown that GPSM2 loss cooperates with activated RasV12 to allow invasion and anchorage independent growth in the human mammary epithelial cell line MCF10A. We have now begun to characterise a role for GPSM2 in the control of mammary progenitor cell clonogenicity and mammary tumourigenesis in vivo and report our findings using both orthotopic xenotransplants and a transgenic mouse model of GPSM2 loss. These studies describe a distinct role for GPSM2 in the hierarchical model of mammary gland development and demonstrate a potential role for GPSM2 in breast cancer.