Role of MAPK pathway oncoproteins in thyroid cancer pathogenesis and as drug targets Journal Article
| Authors: | Knauf, J. A.; Fagin, J. A. |
| Article Title: | Role of MAPK pathway oncoproteins in thyroid cancer pathogenesis and as drug targets |
| Abstract: | Constitutive activation of MAPK in cancer occurs through activating mutations or overexpression of upstream effectors in the pathway, primarily of genes encoding receptor tyrosine kinases, RAS and BRAF. Arguably, the evidence for MAPK activation is most compelling in thyroid cancers and in melanomas. In this review we discuss the mechanisms of tumor development by oncogenic BRAF in these two cancer cell lineages, since this kinase signals preferentially through this pathway. We describe recent information on the mediators of BRAF-induced tumor initiation and escape from senescence. In addition, we review the biochemical events implicated in cellular growth triggered by oncogenic BRAF and the determinants of oncogene addiction. The biology of thyroid cancers induced by oncogenic BRAF is quite distinct, both in humans and in mice. There is great interest in using these insights to design rational new therapies, for which it will become crucial to understand the determinants of sensitivity and resistance to compounds designed to block the pathway. In thyroid cancer, this interest is further heightened by new information on the role of activated BRAF and MAPK pathway activation in disrupting iodine transport and thyroid hormonogenesis. © 2009 Elsevier Ltd. All rights reserved. |
| Keywords: | signal transduction; mitogen activated protein kinase; protein expression; protein phosphorylation; unclassified drug; oncoprotein; pathogenesis; review; nonhuman; antineoplastic agent; protein function; animals; cell viability; mus; cell cycle progression; melanoma; apoptosis; cell growth; map kinase signaling system; protein targeting; antineoplastic activity; carcinogenesis; cancer resistance; disease progression; oncogene proteins; thyroid cancer; thyroid neoplasms; senescence; point mutation; mitogen-activated protein kinases; b raf kinase; 5 (4 bromo 2 chloroanilino) 4 fluoro 1 methyl 1h benzimidazole 6 carbohydroxamic acid 2 hydroxyethyl ester; aal 881; lbt 613; proto-oncogene proteins b-raf |
| Journal Title: | Current Opinion in Cell Biology |
| Volume: | 21 |
| Issue: | 2 |
| ISSN: | 0955-0674 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2009-01-01 |
| Start Page: | 296 |
| End Page: | 303 |
| Language: | English |
| DOI: | 10.1016/j.ceb.2009.01.013 |
| PUBMED: | 19231149 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 13" - "Export Date: 30 November 2010" - "CODEN: COCBE" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work