title: Mammalian target of rapamycin: a central node of complex signaling cascades.
abstract: The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates cell growth and metabolism in response to diverse external stimuli. In the presence of mitogenic stimuli, mTOR transduces signals that activate the translational machinery and promote cell growth. mTOR functions as a central node in a complex net of signaling pathways that are involved both in normal physiological, as well as pathogenic events. mTOR signaling occurs in concert with upstream Akt and tuberous sclerosis complex (TSC) and several downstream effectors. During the past few decades, the mTOR-mediated pathway has been shown to promote tumorigenesis through the coordinated phosphorylation of proteins that directly regulate cell-cycle progression and metabolism, as well as transcription factors that regulate the expression of genes involved in the oncogenic processes. The importance of mTOR signaling in oncology is now widely accepted, and agents that selectively target mTOR have been developed as anti-cancer drugs. In this review, we highlight the past research on mTOR, including clinical and pathological analyses, and describe its molecular mechanisms of signaling, and its roles in the physiology and pathology of human diseases, particularly, lung carcinomas. We also discuss strategies that might lead to more effective clinical treatments of several diseases by targeting mTOR.
authors: Department of Pathology, Respiratory Medicine Saitama, Japan. ydobashi@omiya.jichi.ac.jp
authors: Yoh
authors: Y
authors: Dobashi
authors: Yasutaka
authors: Y
authors: Watanabe
authors: Chihiro
authors: C
authors: Miwa
authors: Sakae
authors: S
authors: Suzuki
authors: Shinichiro
authors: S
authors: Koyama
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D011506:Proteins / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D020123:Sirolimus / Q000494:pharmacology* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
chemical_list: D000903:Antibiotics, Antineoplastic; D046912:Multiprotein Complexes; D011506:Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus