The PI3K-Akt-mTOR pathway in initiation and progression of thyroid tumors.
The phosphoinositide-3 (OH) kinase (PI3K) signaling cascade is involved in regulating glucose uptake and metabolism, growth, motility, and other essential functions for cell survival. Unregulated activation of this pathway commonly occurs in cancer through a variety of mechanisms, including genetic mutations of kinases and regulatory proteins, epigenetic alterations that alter gene expression and translation, and posttranslational modifications. In thyroid cancer, constitutive activation of PI3K signaling has been shown to play a role in the genetic predisposition for thyroid neoplasia in Cowden's syndrome, and is recognized to be frequently overactivated in sporadic forms of thyroid cancer including those with aggressive clinical behaviors. In this review, the key signaling molecules in the PI3K signaling cascade, the abnormalities known to occur in thyroid cancer, and the potential for therapeutic targeting of PI3K pathway members will be discussed.
Saji
Motoyasu
M
Divisions of Endocrinology, Diabetes and Metabolism, The Ohio State University Medical Center, The Ohio State University and The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH, USA.
Ringel
Matthew D
MD
D000818:Animals; D018450:Disease Progression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011230:Precancerous Conditions / Q000201:enzymology* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000473:pathology* / Q000628:therapy
D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human