title: Proline-rich AKT substrate of 40-kDa (PRAS40) in the pathophysiology of cancer.
abstract: Dysregulation of PI3K-AKT-mTOR pathway has been reported in various pathologies, such as cancer and insulin resistance. The proline-rich AKT substrate of 40-kDa (PRAS40), also known as AKT substrate 1 (AKT1S1), lies at the crossroads of these cascades and inhibits the activity of the mTOR complex 1 (mTORC1) kinase. This review discusses the role of PRAS40 and possible feedback mechanisms, and alterations in AKT/PRAS40/mTOR signaling that have been implicated in the pathogenesis of tumor progression. Additionally, we probed new datasets extracted from Oncomine, a cancer microarray database containing datasets derived from patient samples, to further understand the role of PRAS40 (AKT1S1). These data strongly supports the hypothesis that PRAS40 may serve as a potential therapeutic target for various cancers.
authors.affiliation: Department of Physiology and Pharmacology, Thomas J. Long School of Pharmacy and Health Sciences University of the Pacific, Stockton, CA, USA.
authors.forename: Ritu
authors.initials: R
authors.lastname: Malla
authors.affiliation: Department of Pharmaceutical Sciences, St. John's University, Queens, NY, USA.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Ashby
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA.
authors.forename: Narayanan K
authors.initials: NK
authors.lastname: Narayanan
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA.
authors.forename: Bhagavathi
authors.initials: B
authors.lastname: Narayanan
authors.affiliation: Department of Physiology and Pharmacology, Thomas J. Long School of Pharmacy and Health Sciences University of the Pacific, Stockton, CA, USA. Electronic address: jfaridi@pacific.edu.
authors.forename: Jesika S
authors.initials: JS
authors.lastname: Faridi
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, College of Pharmacy & Pharmaceutical Sciences, University of Toledo, OH, USA. Electronic address: amit.tiwari@utoledo.edu.
authors.forename: Amit K
authors.initials: AK
authors.lastname: Tiwari
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D063646:Carcinogenesis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D055808:Drug Discovery; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C484523:AKT1S1 protein, human
keywords: Cancer therapeutics; PI3K/AKT; PRAS40; mTORC1