Portal de investigación
Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Herrero A
- Pinto A
- Colón-Bolea P
- Casar B
- Jones M
- Agudo-Ibáñez L
- Vidal R
- Tenbaum SP
- Nuciforo P
- Valdizán EM
- Horvath Z
- Orfi L
- Bony E
- Keri G
- Rivas G
- Pazos A
- Gozalbes R
- Palmer HG
- Hurlstone A
Grupos
Abstract
Nearly 50% of human malignancies exhibit unregulated RAS-ERK signaling; inhibiting it is a valid strategy for antineoplastic intervention. Upon activation, ERK dimerize, which is essential for ERK extranuclear, but not for nuclear, signaling. Here, we describe a small molecule inhibitor for ERK dimerization that, without affecting ERK phosphorylation, forestalls tumorigenesis driven by RAS-ERK pathway oncogenes. This compound is unaffected by resistance mechanisms that hamper classical RAS-ERK pathway inhibitors. Thus, ERK dimerization inhibitors provide the proof of principle for two understudied concepts in cancer therapy: (1) the blockade of sub-localization-specific sub-signals, rather than total signals, as a means of impeding oncogenic RAS-ERK signaling and (2) targeting regulatory protein-protein interactions, rather than catalytic activities, as an approach for producing effective antitumor agents.
Datos de la publicación
- ISSN/ISSNe:
- 1535-6108, 1878-3686
- Tipo:
- Article
- Páginas:
- 170-182
- Factor de Impacto:
- 13,740 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
Cancer Cell CELL PRESS
Citas Recibidas en Web of Science: 97
Documentos
- No hay documentos
Filiaciones
Keywords
- MUTATIONS CONFER RESISTANCE; MAP KINASE ERK2; ACQUIRED-RESISTANCE; CANCER-THERAPY; COLON-CANCER; BRAF; DIMERS; CELLS; MEK; ACTIVATION
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Cita
Herrero A,Pinto A,Colón P,Casar B,Jones M,Agudo L,Vidal R,Tenbaum SP,Nuciforo P,Valdizán EM,Horvath Z,Orfi L,Pineda A,Bony E,Keri G,Rivas G,Pazos A,Gozalbes R,Palmer HG,Hurlstone A,Crespo P. Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes. Cancer Cell. 2015. 28. (2):p. 170-182. IF:23,214. (1).