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PMID: 19081071 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis.

Developmental cell ·Vol. 15 ·No. 6 ·2008-12-00 ·Pages 813-28

Philippar U, Roussos ET, Oser M, Yamaguchi H, Kim HD, Giampieri S, Wang Y, Goswami S, Wyckoff JB, Lauffenburger DA, Sahai E, Condeelis JS, Gertler FB

Abstract

The spread of cancer during metastatic disease requires that tumor cells subvert normal regulatory networks governing cell motility to invade surrounding tissues and migrate toward blood and lymphatic vessels. Enabled (Ena)/vasodilator-stimulated phosphoprotein (VASP) proteins regulate cell motility by controlling the geometry of assembling actin networks. Mena, an Ena/VASP protein, is upregulated in the invasive subpopulation of breast cancer cells. In addition, Mena is alternately spliced to produce an invasion isoform, Mena(INV). Here we show that Mena and Mena(INV) promote carcinoma cell motility and invasiveness in vivo and in vitro, and increase lung metastasis. Mena and Mena(INV) potentiate epidermal growth factor (EGF)-induced membrane protrusion and increase the matrix degradation activity of tumor cells. Interestingly, Mena(INV) is significantly more effective than Mena in driving metastases and sensitizing cells to EGF-dependent invasion and protrusion. Upregulation of Mena(INV) could therefore enable tumor cells to invade in response to otherwise benign EGF stimulus levels.

MeSH Terms
Alternative Splicing Animals Carcinoma/metabolism Cell Movement Epidermal Growth Factor/metabolism Gene Expression Regulation, Neoplastic Humans Lung Neoplasms/metabolism Macrophages/metabolism Mice Microfilament Proteins/chemistry,physiology Models, Biological Neoplasm Invasiveness Neoplasm Metastasis Neoplasm Transplantation Protein Isoforms
Chemicals
Enah protein, human Microfilament Proteins Protein Isoforms Epidermal Growth Factor
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Philippar Ulrike
Massachusetts Institute of Technology, Koch Institute, Cambridge, MA 02139, USA.
Roussos Evanthia T
Oser Matthew
Yamaguchi Hideki
Kim Hyung-Do
Giampieri Silvia
Wang Yarong
Goswami Sumanta
Wyckoff Jeffrey B
Lauffenburger Douglas A
Sahai Erik
Condeelis John S
Gertler Frank B
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Article Info
Journal
Developmental cell
Abbr.
Dev Cell
ISSN
1878-1551
DOI
10.1016/j.devcel.2008.09.003
Published
2008-12-00
Pages
813-28
Language
English
Region
United States
NLM ID
101120028
PMCID
PMC2637261
Subset
IM
Grants
NCI NIH HHS · P01 CA100324 · United States
NCI NIH HHS · 1-U54-CA112967 · United States
Breast Cancer Now · 2005MAY12 · United Kingdom
NIGMS NIH HHS · GM58801 · United States
NCI NIH HHS · P01 CA100324-01 · United States
NCI NIH HHS · U54 CA112967 · United States
NIGMS NIH HHS · R01 GM058801 · United States
NCI NIH HHS · U54 CA112967-03 · United States
NCI NIH HHS · R01 CA113395 · United States
NIGMS NIH HHS · R01 GM058801-10 · United States
NCI NIH HHS · U54 CA112967-04 · United States
Cancer Research UK · United Kingdom
NIGMS NIH HHS · GM38511 · United States
NCI NIH HHS · CA100324 · United States
NIGMS NIH HHS · R01 GM038511 · United States
NIGMS NIH HHS · R01 GM038511-12 · United States
External Links
PubMed source DOI: 10.1016/j.devcel.2008.09.003 PMC Full Text View journal details
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