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

• Type: Article in International Scientific Journal
• Date: 2015

Authors

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

Journal

Title: Molecular and Cellular Endocrinology

Vol. 415

Pages: 64-75

ISSN: 0303-7207

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 5 Citations

Scopus - 5 Citations

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12