Poster Presentation 30th Lorne Cancer Conference 2018

Control of cell competition by cell shape regulators in tissue development and cancer   (#158)

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

In 1975, Morata and Ripoll described that clones mutant for ribosomal genes (of the Minute loci) are eliminated when surrounded by wild type cells in Drosophila epithelial tissues1. This process was termed “cell competition”, which is defined as a surveillance mechanism that recognizes un-fit or damaged cells and actively eliminates them.

In recent decades, many other genes in Drosophila have been identified as having roles in cell competition, either inhibiting or promoting the competitiveness of cells (reviewed in 2). Cell competition processes are conserved, and, interestingly, many of these genes have mammalian homologues that are proto-oncogenes or tumour suppressors. Much research has examined the possibility of cell competition participating in cancer development; could tumours abuse these mechanisms to overgrow and prevent their removal?

How “winner” cells recognize and eliminate less fit “loser” cells is still poorly understood, but recent work has identified two key molecules. During cell competition induced by polarity disruption, Stranded at second (Sas), a ligand, is expressed and relocalized in “winner” cells, and facilitates the activation of Protein tyrosine phosphatase 10D (Ptp10D), a transmembrane receptor in the “loser cells”, which inhibits EGFR and as a consequence promotes JNK signalling in the polarity-deficient cells, thereby triggering apoptotic pathways3.

Here we present preliminary data from a study that will focus on exploring upstream and downstream elements of the Sas-Ptp10D interplay, when tumour suppressor/cell polarity regulators are impaired in a mosaic setting, in Drosophila and mammalian systems. This research will expand our understanding of how less fit cells are targeted and removed from epithelial tissues during development, how homeostasis is maintained in adult tissues, and whether tumourigenesis is promoted when these mechanisms fail.

  1. Morata G, Ripoll P: Minutes: mutants of Drosophila autonomously affecting cell division rate. Dev. Biol. 1975, 42:211-221.
  2. Baker NE: Mechanisms of cell competition emerging from Drosophila studies. Curr. Biol. 2017, 48:40-46.
  3. Yamamoto M, Ohsawa S, Kunimasa K, Igaki T: The ligand Sas and its receptor PTP10D drive tumour-suppressive cell competition. Nature 2017, 542:246-250.