Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/50155

TitleRAF-1 promotes survival of thyroid cancer cells harboring RET/PTC1 rearrangement independently of ERK activation
Author(s)Castro, Lisandra
Alves, Sara
Chaves, Susana R.
Costa, Jose Luis
Soares, Paula
Preto, Ana
KeywordsThyroid cancer
RAF-1
BRAF
RET/PTC1
PI3K-AKT
ERK
Issue date5-Nov-2015
PublisherElsevier
JournalMolecular and Cellular Endocrinology
Abstract(s)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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
TypeArticle
URIhttp://hdl.handle.net/1822/50155
DOI10.1016/j.mce.2015.08.006
ISSN0303-7207
e-ISSN1872-8057
Peer-Reviewedyes
AccessRestricted access (Author)
Appears in Collections:DBio - Artigos/Papers

Files in This Item:
File Description SizeFormat 
Castro L MCE last 1-s2.0-S0303720715300460-main 22 set15.pdf
  Restricted access
3,45 MBAdobe PDFView/Open    Request a copy!

Partilhe no FacebookPartilhe no TwitterPartilhe no DeliciousPartilhe no LinkedInPartilhe no DiggAdicionar ao Google BookmarksPartilhe no MySpacePartilhe no Orkut
Exporte no formato BibTex mendeley Exporte no formato Endnote Adicione ao seu ORCID