Oncogenic BRAF-Mediated Melanoma Cell Invasion.
Cell Rep
; 15(9): 2012-24, 2016 05 31.
Article
in En
| MEDLINE
| ID: mdl-27210749
ABSTRACT
Melanoma patients with oncogenic BRAF(V600E) mutation have poor prognoses. While the role of BRAF(V600E) in tumorigenesis is well established, its involvement in metastasis that is clinically observed in melanoma patients remains a topic of debate. Here, we show that BRAF(V600E) melanoma cells have extensive invasion activity as assayed by the generation of F-actin and cortactin foci that mediate membrane protrusion, and degradation of the extracellular matrix (ECM). Inhibition of BRAF(V600E) blocks melanoma cell invasion. In a BRAF(V600E)-driven murine melanoma model or in patients' tumor biopsies, cortactin foci decrease upon inhibitor treatment. In addition, genome-wide expression analysis shows that a number of invadopodia-related genes are downregulated after BRAF(V600E) inhibition. Mechanistically, BRAF(V600E) induces phosphorylation of cortactin and the exocyst subunit Exo70 through ERK, which regulates actin dynamics and matrix metalloprotease secretion, respectively. Our results provide support for the role of BRAF(V600E) in metastasis and suggest that inhibiting invasion is a potential therapeutic strategy against melanoma.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oncogenes
/
Skin Neoplasms
/
Proto-Oncogene Proteins B-raf
/
Melanoma
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Rep
Year:
2016
Document type:
Article
Affiliation country:
Estados Unidos