RRC ID 47453
Author Yamamoto M, Ohsawa S, Kunimasa K, Igaki T.
Title The ligand Sas and its receptor PTP10D drive tumour-suppressive cell competition.
Journal Nature
Abstract Normal epithelial cells often exert anti-tumour effects against nearby oncogenic cells. In the Drosophila imaginal epithelium, clones of oncogenic cells with loss-of-function mutations in the apico-basal polarity genes scribble or discs large are actively eliminated by cell competition when surrounded by wild-type cells. Although c-Jun N-terminal kinase (JNK) signalling plays a crucial role in this cell elimination, the initial event, which occurs at the interface between normal cells and polarity-deficient cells, has not previously been identified. Here, through a genetic screen in Drosophila, we identify the ligand Sas and the receptor-type tyrosine phosphatase PTP10D as the cell-surface ligand-receptor system that drives tumour-suppressive cell competition. At the interface between the wild-type 'winner' and the polarity-deficient 'loser' clones, winner cells relocalize Sas to the lateral cell surface, whereas loser cells relocalize PTP10D there. This leads to the trans-activation of Sas-PTP10D signalling in loser cells, which restrains EGFR signalling and thereby enables elevated JNK signalling in loser cells, triggering cell elimination. In the absence of Sas-PTP10D, elevated EGFR signalling in loser cells switches the role of JNK from pro-apoptotic to pro-proliferative by inactivating the Hippo pathway, thereby driving the overgrowth of polarity-deficient cells. These findings uncover the mechanism by which normal epithelial cells recognize oncogenic polarity-deficient neighbours to drive cell competition.
Volume 542(7640)
Pages 246-250
Published 2017-2-9
DOI 10.1038/nature21033
PII nature21033
PMID 28092921
MeSH Animals Apoptosis Cell Polarity Cell Proliferation Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / cytology* Drosophila melanogaster / genetics Drosophila melanogaster / metabolism* Epithelial Cells / cytology Epithelial Cells / metabolism ErbB Receptors / metabolism Female JNK Mitogen-Activated Protein Kinases / metabolism Ligands Male Membrane Proteins / genetics Neoplasms / metabolism Neoplasms / pathology* Protein Tyrosine Phosphatases / metabolism* Receptors, Cell Surface / metabolism* Signal Transduction Transcriptional Activation Tumor Suppressor Proteins / genetics
IF 43.07
Times Cited 58
WOS Category CELL BIOLOGY
Resource
Drosophila