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

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.
Authors	Ulrike Philippar, Evanthia T Roussos, Matthew Oser, Hideki Yamaguchi, Hyung-Do Kim, Silvia Giampieri, Yarong Wang, Sumanta Goswami, Jeffrey B Wyckoff, Douglas A Lauffenburger, Erik Sahai, John S Condeelis, Frank B Gertler
Journal	Developmental cell (Dev Cell) Vol. 15 Issue 6 Pg. 813-28 (Dec 2008) ISSN: 1878-1551 [Electronic] United States
PMID	19081071 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Enah protein, human Microfilament Proteins Protein Isoforms Epidermal Growth Factor
Topics	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

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!