A1 Refereed original research article in a scientific journal
Loss of ADAM9 expression impairs beta 1 integrin endocytosis, focal adhesion formation and cancer cell migration
Authors: Mygind KJ, Schwarz J, Sahgal P, Ivaska J, Kveiborg M
Publisher: COMPANY OF BIOLOGISTS LTD
Publication year: 2018
Journal: Journal of Cell Science
Journal name in source: JOURNAL OF CELL SCIENCE
Journal acronym: J CELL SCI
Article number: UNSP jcs205393
Volume: 131
Issue: 1
Number of pages: 12
ISSN: 0021-9533
eISSN: 1477-9137
DOI: https://doi.org/10.1242/jcs.205393
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/30228108
The transmembrane protease ADAM9 is frequently upregulated in human cancers, and it promotes tumour progression in mice. In vitro, ADAM9 regulates cancer cell adhesion and migration by interacting with integrins. However, how ADAM9 modulates integrin functions is not known. We here show that ADAM9 knockdown increases beta 1 integrin levels through mechanisms that are independent of its protease activity, in ADAM9-silenced cells, adhesion to collagen and fibronectin is reduced, suggesting an altered function of the accumulated integrins. Mechanistically, ADAM9 co-immunoprecipitates with beta 1 integrin, and both internalization and subsequent degradation of beta 1 integrin are significantly decreased in ADAM9-silenced cells, with no effect on beta 1 integrin recycling. Accordingly, the formation of focal adhesions and actin stress fibres in ADAM9-silenced cells is altered, possibly explaining the reduction in cell adhesion and migration in these cells. Taken together, our data provide mechanistic insight into the ADAM9-integrin interaction, demonstrating that ADAM9 regulates beta 1 integrin endocytosis. Moreover, our findings indicate that the reduced migration of ADAM9-silenced cells is, at least in part, caused by the accumulation and altered activity of beta 1 integrin at the cell surface.
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