Universität zu Köln

Armistead, Joy, Hatzold, Julia ORCID: 0000-0002-5491-1921, van Roye, Anna, Fahle, Evelin and Hammerschmidt, Matthias (2020). Entosis and apical cell extrusion constitute a tumor-suppressive mechanism downstream of Matriptase. J. Cell Biol., 219 (2). NEW YORK: ROCKEFELLER UNIV PRESS. ISSN 1540-8140

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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-offunction 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Armistead, Joy UNSPECIFIED UNSPECIFIED UNSPECIFIED Hatzold, Julia UNSPECIFIED orcid.org/0000-0002-5491-1921 UNSPECIFIED van Roye, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Fahle, Evelin UNSPECIFIED UNSPECIFIED UNSPECIFIED Hammerschmidt, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-345563
DOI:	10.1083/jcb.201905190
Journal or Publication Title:	J. Cell Biol.
Volume:	219
Number:	2
Date:	2020
Publisher:	ROCKEFELLER UNIV PRESS
Place of Publication:	NEW YORK
ISSN:	1540-8140
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language APOPTOTIC EPITHELIAL-CELLS; HEPATOCYTE GROWTH-FACTOR; PHOSPHATIDIC-ACID; SPHINGOSINE KINASE-1; TRANSGENIC ZEBRAFISH; CANCER; SPHINGOSINE-1-PHOSPHATE; RECEPTOR; ACTIVATION; INHIBITORS Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/34556