Regulation and importance of the PI3K/Akt/mTOR signaling pathway in hematologic malignancies.
Phosphatidylinositol 3-kinase (PI3K), a heterodimeric lipid kinase, is a key enzyme in signal transduction from various stimuli to downstream pathways that elicit diverse responses involving growth, proliferation, survival, differentiation, and metabolism in many cellular systems. Activated PI3K generates phosphatidylinositol-3,4,5-triphosphate, which recruits phosphatidylinositol-dependent kinase 1 (PDK1) and Akt serine/threonine kinase at the plasma membrane, resulting in activation of Akt. In turn, Akt activates multiple downstream targets, most notably the mTOR pathway. There is abundant evidence implicating the PI3K/Akt/mTOR pathway in the development and progression of a variety of tumors including hematologic neoplasms. Therefore, this pathway is considered a critical target for cancer therapy. We review the regulatory mechanisms of the PI3K/Akt/mTOR signaling pathway and the role of this pathway in oncogenesis of hematological malignancies.
Kawauchi
Kiyotaka
K
Department of Medicine, Tokyo Women's Medical University Medical Center East, Japan. ochamegm@dnh.twmu.ac.jp
Ogasawara
Toshie
T
Yasuyama
Masako
M
Otsuka
Kuniaki
K
Yamada
Osamu
O
D019337:Hematologic Neoplasms / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases
D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human