A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis.
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.
Philippar
Ulrike
U
Massachusetts Institute of Technology, Koch Institute, Cambridge, MA 02139, USA.
Roussos
Evanthia T
ET
Oser
Matthew
M
Yamaguchi
Hideki
H
Kim
Hyung-Do
HD
Giampieri
Silvia
S
Wang
Yarong
Y
Goswami
Sumanta
S
Wyckoff
Jeffrey B
JB
Lauffenburger
Douglas A
DA
Sahai
Erik
E
Condeelis
John S
JS
Gertler
Frank B
FB
D017398:Alternative Splicing; D000818:Animals; D002277:Carcinoma / Q000378:metabolism*; D002465:Cell Movement; D004815:Epidermal Growth Factor / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry* / Q000502:physiology*; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D020033:Protein Isoforms
C511939:Enah protein, human; D008840:Microfilament Proteins; D020033:Protein Isoforms; D004815:Epidermal Growth Factor