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Entosis and apical cell extrusion constitute a tumor-suppressive mechanism downstream of Matriptase.
Entosis and apical cell extrusion constitute a tumor-suppressive mechanism downstream of Matriptase.
- Source :
-
The Journal of cell biology [J Cell Biol] 2020 Feb 03; Vol. 219 (2). - Publication Year :
- 2020
-
Abstract
- The type II transmembrane serine protease Matriptase 1 (ST14) is commonly known as an oncogene, yet it also plays an understudied role in suppressing carcinogenesis. This double face is evident in the embryonic epidermis of zebrafish loss-of-function mutants in the cognate Matriptase inhibitor Hai1a (Spint1a). Mutant embryos display epidermal hyperplasia, but also apical cell extrusions, during which extruding outer keratinocytes carry out an entosis-like engulfment and entrainment of underlying basal cells, constituting a tumor-suppressive effect. These counteracting Matriptase effects depend on EGFR and the newly identified mediator phospholipase D (PLD), which promotes both mTORC1-dependent cell proliferation and sphingosine-1-phosphate (S1P)-dependent entosis and apical cell extrusion. Accordingly, hypomorphic hai1a mutants heal spontaneously, while otherwise lethal hai1a amorphs are efficiently rescued upon cotreatment with PLD inhibitors and S1P. Together, our data elucidate the mechanisms underlying the double face of Matriptase function in vivo and reveal the potential use of combinatorial carcinoma treatments when such double-face mechanisms are involved.<br /> (© 2019 Armistead et al.)
- Subjects :
- Animals
Carcinogenesis genetics
Cell Proliferation genetics
Disease Models, Animal
Embryonic Development genetics
Epidermis growth & development
Epidermis pathology
ErbB Receptors genetics
Genes, Tumor Suppressor
Humans
Hyperplasia pathology
Keratinocytes metabolism
Keratinocytes pathology
Loss of Function Mutation genetics
Lysophospholipids genetics
Lysophospholipids metabolism
Mechanistic Target of Rapamycin Complex 1 genetics
Phospholipase D genetics
Sphingosine analogs & derivatives
Sphingosine genetics
Sphingosine metabolism
Zebrafish genetics
Entosis genetics
Hyperplasia genetics
Proteinase Inhibitory Proteins, Secretory genetics
Serine Endopeptidases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1540-8140
- Volume :
- 219
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 31819976
- Full Text :
- https://doi.org/10.1083/jcb.201905190