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Type: Journal article
Title: Cytoskeletal protein flightless I inhibits apoptosis, enhances tumor cell invasion and promotes cutaneous squamous cell carcinoma progression
Author: Kopecki, Z.
Yang, G.
Jackson, J.
Melville, E.
Caley, M.
Murrell, D.
Darby, I.
O'Toole, E.
Samuel, M.
Cowin, A.
Citation: Oncotarget, 2015; 6(34):36426-36440
Publisher: Impact Journals
Issue Date: 2015
ISSN: 1949-2553
Statement of
Zlatko Kopecki, Gink N. Yang, Jessica E. Jackson, Elizabeth L. Melville, Matthew P. Caley, Dedee F. Murrell, Ian A. Darby, Edel A. O, Toole, Michael S. Samuel, Allison J. Cowin
Abstract: Flightless I (Flii) is an actin remodeling protein that affects cellular processes including adhesion, proliferation and migration. In order to determine the role of Flii during carcinogenesis, squamous cell carcinomas (SCCs) were induced in Flii heterozygous (Flii+/-), wild-type and Flii overexpressing (FliiTg/Tg) mice by intradermal injection of 3-methylcholanthrene (MCA). Flii levels were further assessed in biopsies from human SCCs and the human SCC cell line (MET-1) was used to determine the effect of Flii on cellular invasion. Flii was highly expressed in human SCC biopsies particularly by the invading cells at the tumor edge. FliiTg/Tg mice developed large, aggressive SCCs in response to MCA. In contrast Flii+/- mice had significantly smaller tumors that were less invasive. Intradermal injection of Flii neutralizing antibodies during SCC initiation and progression significantly reduced the size of the tumors and, in vitro, decreased cellular sphere formation and invasion. Analysis of the tumors from the Flii overexpressing mice showed reduced caspase I and annexin V expression suggesting Flii may negatively regulate apoptosis within these tumors. These studies therefore suggest that Flii enhances SCC tumor progression by decreasing apoptosis and enhancing tumor cell invasion. Targeting Flii may be a potential strategy for reducing the severity of SCCs.
Keywords: Flightless; squamous cell carcinoma; cell invasion; skin cancer
Description: Published: October 19, 2015
Rights: Copyright @ 2016 Impact Journals, LLC. All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
DOI: 10.18632/oncotarget.5536
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Pathology publications

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