WIP and WICH/WIRE co-ordinately control invadopodium formation and maturation in human breast cancer cell invasion
Author(s)
Type
Journal Article
Abstract
Cancer cells form actin-rich degradative protrusions (invasive pseudopods and invadopodia), which
allows their efficient dispersal during metastasis. Using biochemical and advanced imaging approaches,
we demonstrate that the N-WASP-interactors WIP and WICH/WIRE play non-redundant roles in
cancer cell invasion. WIP interacts with N-WASP and cortactin and is essential for invadopodium
assembly, whereas WICH/WIRE regulates N-WASP activation to control invadopodium maturation
and degradative activity. Our data also show that Nck interaction with WIP and WICH/WIRE modulates
invadopodium maturation; changes in WIP and WICH/WIRE levels induce differential distribution of
Nck. We show that WIP can replace WICH/WIRE functions and that elevated WIP levels correlate with
high invasiveness. These findings identify a role for WICH/WIRE in invasiveness and highlight WIP as
a hub for signaling molecule recruitment during invadopodium generation and cancer progression, as
well as a potential diagnostic biomarker and an optimal target for therapeutic approaches.
allows their efficient dispersal during metastasis. Using biochemical and advanced imaging approaches,
we demonstrate that the N-WASP-interactors WIP and WICH/WIRE play non-redundant roles in
cancer cell invasion. WIP interacts with N-WASP and cortactin and is essential for invadopodium
assembly, whereas WICH/WIRE regulates N-WASP activation to control invadopodium maturation
and degradative activity. Our data also show that Nck interaction with WIP and WICH/WIRE modulates
invadopodium maturation; changes in WIP and WICH/WIRE levels induce differential distribution of
Nck. We show that WIP can replace WICH/WIRE functions and that elevated WIP levels correlate with
high invasiveness. These findings identify a role for WICH/WIRE in invasiveness and highlight WIP as
a hub for signaling molecule recruitment during invadopodium generation and cancer progression, as
well as a potential diagnostic biomarker and an optimal target for therapeutic approaches.
Date Issued
2016-03-24
Date Acceptance
2016-03-08
Citation
Scientific Reports, 2016, 6
ISSN
2045-2322
Publisher
Nature Research (part of Springer Nature)
Journal / Book Title
Scientific Reports
Volume
6
Copyright Statement
© 2016 The Author(s). This work is licensed under a Creative Commons Attribution 4.0 International License. The images
or other third party material in this article are included in the article’s Creative Commons license,
unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material. To view a copy of this
license, visit http://creativecommons.org/licenses/by/4.0/.
or other third party material in this article are included in the article’s Creative Commons license,
unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material. To view a copy of this
license, visit http://creativecommons.org/licenses/by/4.0/.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000372698800001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
EXTRACELLULAR-MATRIX DEGRADATION
EPITHELIAL-MESENCHYMAL TRANSITION
ALDRICH-SYNDROME PROTEIN
ACTIN-FILAMENT SYSTEM
BASAL-LIKE PHENOTYPE
N-WASP
FOCAL ADHESIONS
IN-VITRO
TYROSINE PHOSPHORYLATION
MAMMALIAN VERPROLIN
Publication Status
Published
Article Number
23590
Date Publish Online
2016-03-24