RAF-1 promotes survival of thyroid cancer cells harboring RET/PTC1 rearrangement independently of ERK activation

• Tipo: Artigo em Revista Científica Internacional
• Data: 2015

Autores

Lisandra Castro (Autor) Outra; Sara Alves (Autor) Outra; Susana R Chaves (Autor) Outra; Jose Luis Costa (Autor) Outra; Paula Soares (Autor) FMUP; Ana Preto (Autor) Outra

Revista

Título: Molecular and Cellular Endocrinology

Vol. 415

Páginas: 64-75

ISSN: 0303-7207

Editora: Elsevier

Indexação

ISI Web of Knowledge - 5 Citações

Scopus - 5 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina clínica

Outras Informações

ID Authenticus: P-00G-P5H

DOI: 10.1016/j.mce.2015.08.006

Abstract (EN): Thyroid cancer (TC) is frequently associated with BRAF or RAS oncogenic mutations and RET/PTC rear-rangements, with aberrant RAF-MEK-ERK and/or PI3K pathway activation. BRAF underlies ERR activation in most TC cells, but not in TPC-1 cells with RET/PTC1 rearrangement. Here, we show that depletion of RAF-1, a RAF family member with a poorly defined role in TC, decreases proliferation and increases apoptosis in TPC-1 cells and, less significantly, in cells harboring a BRAF(V600E) or HRAS(G13R) mutations, but without affecting ERR activation. We further demonstrate that constitutive activation of ERKs in TPC-1 cells is not caused by mutations in 50 oncogenes and tumor suppressors prone to activate the ERR pathway, or affected by inhibition of BRAF, MEK1/2 or PI3K. Our data indicate that RAF-1 is important for the survival of TPC-1 cells independently of the classical MEK1/2-ERK activation, offering new perspectives on RET/PTC signaling and for the therapy of thyroid cancers.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 12