[Intracellular signaling mechanisms in thyroid cancer]

Cir Cir. 2016 Sep-Oct;84(5):434-43. doi: 10.1016/j.circir.2016.05.017. Epub 2016 Aug 8.
[Article in Spanish]

Abstract

Background: Thyroid cancer is the most common malignancy of the endocrine system, the papillary variant accounts for 80-90% of all diagnosed cases. In the development of papillary thyroid cancer, BRAF and RAS genes are mainly affected, resulting in a modification of the system of intracellular signaling proteins known as «protein kinase mitogen-activated» (MAPK) which consist of «modules» of internal signaling proteins (Receptor/Ras/Raf/MEK/ERK) from the cell membrane to the nucleus. In thyroid cancer, these signanling proteins regulate diverse cellular processes such as differentiation, growth, development and apoptosis. MAPK play an important role in the pathogenesis of thyroid cancer as they are used as molecular biomarkers for diagnostic, prognostic and as possible therapeutic molecular targets. Mutations in BRAF gene have been correlated with poor response to treatment with traditional chemotherapy and as an indicator of poor prognosis.

Objective: To review the molecular mechanisms involved in intracellular signaling of BRAF and RAS genes in thyroid cancer.

Conclusions: Molecular therapy research is in progress for this type of cancer as new molecules have been developed in order to inhibit any of the components of the signaling pathway (RET/PTC)/Ras/Raf/MEK/ERK; with special emphasis on the (RET/PTC)/Ras/Raf section, which is a major effector of ERK pathway.

Keywords: BRAF mutations; Cinasas de proteínas activadas por mitógenos MAPK; Cáncer de tiroides; Mitogenactivated protein kinase MAPK; Mutaciones BRAF; Thyroid cancer.

Publication types

  • Review

MeSH terms

  • Cell Transformation, Neoplastic
  • Genes, Neoplasm
  • Genes, ras
  • Humans
  • MAP Kinase Signaling System
  • Molecular Targeted Therapy
  • Mutation
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • PAX8 Transcription Factor / genetics
  • PAX8 Transcription Factor / physiology
  • PPAR gamma / genetics
  • PPAR gamma / physiology
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / physiology
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins B-raf / physiology
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / physiology
  • Signal Transduction* / genetics
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / physiology
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism*
  • Thyroid Neoplasms / therapy

Substances

  • Neoplasm Proteins
  • PAX8 Transcription Factor
  • PAX8 protein, human
  • PPAR gamma
  • MTOR protein, human
  • AKT1 protein, human
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases