Cell competition is a surveillance mechanism where tissue homeostasis is maintained by the elimination of “less fit” cells by their “more fit” neighbours. First identified in Drosophila melanogaster, it has since been shown to be conserved in mammalian systems, as are many of the genes involved.
Cell competition can occur via a cell acquiring a mutation that promotes its fitness relative to its neighbours, such as through increased ribosome biogenesis or proliferative capacity – activating mutations in genes like myc, yki, or Stat92E can contribute to these phenotypes – and in these instances, the mutant cell will outcompete and actively eliminate its wildtype neighbours by caspase-mediated cell death. However, the converse is also true: a cell can acquire a mutation that renders it less fit relative to its neighbours – such as a disruption to one of the cell polarity regulators; scrib, l(2)gl, or dlg1 – and this cell would then be actively eliminated by its wildtype neighbours.
In polarity-impaired cells, JNK signalling in the less fit cells promotes their apoptosis, and also leads to the expression and secretion of the Upd (IL6) family ligands, which activate Jak-STAT signalling in the surrounding wildtype cells, promoting their compensatory proliferation to replace the mutant cells. However, Upd is capable of acting in an autocrine manner, and promoting proliferation of the cells in which it is originally expressed. Why, then, does this not occur in polarity-impaired cells?
Differential expression of Protein tyrosine phosphatase 61F (Ptp61F) may be the answer. Ptp61F is a phosphatase that can inhibit the Jak-STAT signalling pathway, and which has mammalian orthologues (PTP1B and TCPTP) downregulated in various cancers. Ptp61F overexpression is capable of reducing Jak-STAT signalling-induced tissue overgrowth, and clones mutant for Ptp61F possess a competitive advantage over wildtype clones. Thus, we believe that Ptp61F is more highly expressed or active in less fit, scrib mutant cells, inhibiting Jak-STAT signalling and promoting their elimination.