Universität zu Köln

Kulshammer, Eva ORCID: 0000-0002-3208-0872, Kilinc, Merve, Csordas, Gabor ORCID: 0000-0001-6871-6839, Bresser, Tina, Nolte, Hendrik and Uhlirova, Mirka ORCID: 0000-0002-5735-8287 (2022). The mechanosensor Filamin A/Cheerio promotes tumourigenesis via specific interactions with components of the cell cortex. FEBS J., 289 (15). S. 4497 - 4518. HOBOKEN: WILEY. ISSN 1742-4658

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Abstract

Cancer development has been linked to aberrant sensing and interpretation of mechanical cues and force-generating properties. Here, we show that upregulation of the actin crosslinking protein Cheerio (Cher), the fly ortholog of Filamin A (FLNA), and the conformation of its mechanosensitive region (MSR) are instrumental to the malignancy of polarity-deficient, Ras-driven tumours in Drosophila epithelia. We demonstrate that impaired growth and cytoskeletal contractility of tumours devoid of cher can be rescued by stimulating myosin activity. Profiling the Cher interactome in tumour-bearing imaginal discs identified several components of the cell cortex, including the beta-heavy Spectrin Karst (Kst), the scaffolding protein Big bang (Bbg), and 14-3-3 epsilon. We show that Cher binds Bbg through the MSR while the interaction with 14-3-3 epsilon and Kst is MSR-independent. Importantly, our genetic studies define Bbg, Kst, and 14-3-3 epsilon as tumour suppressors. The tumour-promoting function of Cher thus relies on its capacity to control the contractile state of the cytoskeleton through interactions with myosin and specific components of the cell cortex.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kulshammer, Eva UNSPECIFIED orcid.org/0000-0002-3208-0872 UNSPECIFIED Kilinc, Merve UNSPECIFIED UNSPECIFIED UNSPECIFIED Csordas, Gabor UNSPECIFIED orcid.org/0000-0001-6871-6839 UNSPECIFIED Bresser, Tina UNSPECIFIED UNSPECIFIED UNSPECIFIED Nolte, Hendrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Uhlirova, Mirka UNSPECIFIED orcid.org/0000-0002-5735-8287 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-658872
DOI:	10.1111/febs.16408
Journal or Publication Title:	FEBS J.
Volume:	289
Number:	15
Page Range:	S. 4497 - 4518
Date:	2022
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1742-4658
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DROSOPHILA; MECHANICS; SPECTRIN; GROWTH; PROLIFERATION; DOWNSTREAM; ORGANIZERS; INVASION; BINDING; FILGAP Multiple languages Biochemistry & Molecular Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/65887