Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/8144
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Overexpression of Akt converts radial growth melanoma to vertical growth melanoma |
Autor: | Govindarajan, Baskaran; Sligh, James E.; Vincent, Bethaney J.; Li, Meiling; Canter, Jeffrey A.; Nickoloff, Brian J.; Rodenburg, Richard J.; Smeitink, Jan A.; Oberley, Larry; Zhang, Yuping; Slingerland, Joyce; Arnold, Rebecca S.; Lambeth, J. David; Cohen, Cynthia; Hilenski, Lu; Griendling, Kathy; Martínez-Díez, Marta; Cuezva, José M. CSIC ORCID; Arbiser, Jack L. | Palabras clave: | Melanoma growth | Fecha de publicación: | 22-feb-2007 | Editor: | American Society for Clinical Investigation | Citación: | J. Clin. Invest. 117(3): 719-729 (2007) | Resumen: | Melanoma is the cancer with the highest increase in incidence, and transformation of radial growth to vertical growth (i.e., noninvasive to invasive) melanoma is required for invasive disease and metastasis. We have previously shown that p42/p44 MAP kinase is activated in radial growth melanoma, suggesting that further signaling events are required for vertical growth melanoma. The molecular events that accompany this transformation are not well understood. Akt, a signaling molecule downstream of PI3K, was introduced into the radial growth WM35 melanoma in order to test whether Akt overexpression is sufficient to accomplish this transformation. Overexpression of Akt led to upregulation of VEGF, increased production of superoxide ROS, and the switch to a more pronounced glycolytic metabolism. Subcutaneous implantation of WM35 cells overexpressing Akt led to rapidly growing tumors in vivo, while vector control cells did not form tumors. We demonstrated that Akt was associated with malignant transformation of melanoma through at least 2 mechanisms. First, Akt may stabilize cells with extensive mitochondrial DNA mutation, which can generate ROS. Second, Akt can induce expression of the ROS-generating enzyme NOX4. Akt thus serves as a molecular switch that increases angiogenesis and the generation of superoxide, fostering more aggressive tumor behavior. Targeting Akt and ROS may be of therapeutic importance in treatment of advanced melanoma | Versión del editor: | http://dx.doi.org/10.1172/JCI30102 | URI: | http://hdl.handle.net/10261/8144 | DOI: | 10.1172/JCI30102 | ISSN: | 0021-9738 | E-ISSN: | 1558-8238 |
Aparece en las colecciones: | (CBM) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
BGovindarajan_JClinInvest_719.pdf | Main text | 750,49 kB | Adobe PDF | Visualizar/Abrir |
BGovindarajan_JClinInvest_Supplmentary.pdf | 474,06 kB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
PubMed Central
Citations
120
checked on 06-mar-2024
SCOPUSTM
Citations
234
checked on 20-mar-2024
WEB OF SCIENCETM
Citations
217
checked on 29-feb-2024
Page view(s)
459
checked on 28-mar-2024
Download(s)
444
checked on 28-mar-2024
Google ScholarTM
Check
Altmetric
Altmetric
Artículos relacionados:
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.