Poster Presentation 40th Annual Lorne Genome Conference 2019

Control of cell competition by cell shape regulators in tissue development and cancer (#148)

Natasha Fahey-Lozano 1 , John E La Marca 1 , Helena E Richardson 1
  1. La Trobe Institute for Molecular Sciences, Bundoora, VICTORIA, Australia

Cell competition (CC) is an important surveillance mechanism that measures relative fitness in a tissue during development and homeostasis. Fitter cells (winner cells) eliminate less fit cells (loser cells), which would otherwise survive in a homozygous (all mutant) tissue. CC was originally described in the Drosophila larvae imaginal discs, since then many genes and signalling pathways have been discovered to be involved in CC. One type of CC involves the polarity genes scribble (scrib), disc large (dlg) and lethal giant larvae (lgl) (which are also tumour suppressors) and give the cells a loser fate if surrounded by wild type cells. In the case of scrib and dlg, wild type cells surrounding them use the SAS ligand to activate PTP10D, a receptor tyrosine phosphatase, in the polarity disrupted cells. Without PTP10D signalling, EGFR is hyperactivated in polarity disrupted cells and it synergizes with JNK signalling to inhibit hippo pathway and promote proliferation, survival and tumorigenesis.  We are using a Drosophila model to investigate the role of the PTP10D-SAS system in other cell polarity and cell shape disruptions. We are also investigating the possible participation of other signalling pathways in the elimination of loser cells. Additionally we are carrying out studies in mammalian cell culture to understand if this mechanism is conserved.