Reference - Detail
| 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 | 42.779 |
| Times Cited | 58 |
| WOS Category | CELL BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 64 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Drosophila | |