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Journal article
Oncogenic BRAF-Mediated Melanoma Cell Invasion
Cell reports (Cambridge), v 15(9), pp 2012-2024
31 May 2016
PMID: 27210749
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Melanoma patients with oncogenic BRAFV600E mutation have poor prognoses. While the role of BRAFV600E 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 BRAFV600E 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 BRAFV600E blocks melanoma cell invasion. In a BRAFV600E-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 BRAFV600E inhibition. Mechanistically, BRAFV600E 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 BRAFV600E in metastasis and suggest that inhibiting invasion is a potential therapeutic strategy against melanoma.
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•BRAFV600E is involved in promoting melanoma cell invasion•BRAFV600E induces the phosphorylation of cortactin and Exo70 through ERK•Inhibiting BRAFV600E reduces invasion-related gene expression in a BRAF mouse model•BRAFV600E inhibition reduces cortactin foci formation in melanoma patient samples
Lu et al. show that BRAFV600E melanoma have extensive actin-based membrane protrusions and ECM degradation activity, which are mediated by ERK phosphorylation of cortactin and Exo70. The study implicates BRAFV600E in melanoma invasion, in addition to its well-established role in tumorigenesis.
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Details
- Title
- Oncogenic BRAF-Mediated Melanoma Cell Invasion
- Creators
- Hezhe Lu - University of PennsylvaniaShujing Liu - University of PennsylvaniaGao Zhang - The Wistar InstituteLawrence N. Kwong - Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 770303, USAYueyao Zhu - University of PennsylvaniaJohn P. Miller - Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 770303, USAYi Hu - Drexel UniversityWenqun Zhong - University of PennsylvaniaJingwen Zeng - University of PennsylvaniaLawrence Wu - The Wistar InstituteClemens Krepler - The Wistar InstituteKatrin Sproesser - The Wistar InstituteMin Xiao - The Wistar InstituteWei Xu - University of PennsylvaniaGiorgos C. Karakousis - Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USALynn M. Schuchter - Abramson Cancer Center and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USAJeffery Field - Translational TherapeuticsPaul J. Zhang - Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USAMeenhard Herlyn - The Wistar InstituteXiaowei Xu - University of PennsylvaniaWei Guo - University of Pennsylvania
- Publication Details
- Cell reports (Cambridge), v 15(9), pp 2012-2024
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000376887500015
- Scopus ID
- 2-s2.0-84971224778
- Other Identifier
- 991019167636104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology