MAPK Signaling Cascade in Papillary Thyroid Carcinoma

Schematic representation of the MAPK signaling cascade in papillary thyroid carcinoma
  • MAPK, also known as ERK:
    • Translocates to the nucleus and promotes cell division:
      • When it is phosphorylated by MEK:
        • A serine / threonine kinase
    • Constitutive activation of this process:
      • Is tumorigenic
  • MAPK phosphorylation is a relatively distal step in a sequential phosphorylation cascade:
    • That can begin with the activation of a tyrosine kinase:
      • Is followed by phosphorylation of RAS:
        • Which activates BRAF:
          • A serine / threonine kinase
      • This is followed by MEK and MAPK phosphorylation
  • In papillary thyroid carcinoma:
    • Somatic genetic alterations at three of these steps:
      • Activate this linear signaling cascade
  • A gene rearrangement:
    • Creating a chimeric RET or TRK activates the initial tyrosine kinase step
  • Activating point mutations of either RAS or BRAF:
    • Constitutively activates these proteins
  • The tyrosine kinase, RAS, and BRAF genetic alterations:
    • Are usually mutually exclusive, suggesting that any single alteration is sufficient to play an early role in tumorigenesis

#Arrangoiz #ThyroidSurgeon #CancerSurgeon #ThyroidExpert #SurgicalOncologist #HeadandNeckSurgeon #MountSinaiMedicalCenter #Miami #Mexico

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