Proline-rich AKT substrate of 40-kDa (PRAS40) in the pathophysiology of cancer

Ritu Malla; Charles R Ashby Jr; Narayanan K Narayanan; Bhagavathi Narayanan; Jesika S Faridi; Amit K Tiwari

doi:10.1016/j.bbrc.2015.05.041

Proline-rich AKT substrate of 40-kDa (PRAS40) in the pathophysiology of cancer

Biochem Biophys Res Commun. 2015 Jul 31;463(3):161-6. doi: 10.1016/j.bbrc.2015.05.041. Epub 2015 May 20.

Authors

Ritu Malla¹, Charles R Ashby Jr², Narayanan K Narayanan³, Bhagavathi Narayanan³, Jesika S Faridi⁴, Amit K Tiwari⁵

Affiliations

¹ Department of Physiology and Pharmacology, Thomas J. Long School of Pharmacy and Health Sciences University of the Pacific, Stockton, CA, USA.
² Department of Pharmaceutical Sciences, St. John's University, Queens, NY, USA.
³ Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA.
⁴ 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.
⁵ Department of Pharmacology and Experimental Therapeutics, College of Pharmacy & Pharmaceutical Sciences, University of Toledo, OH, USA. Electronic address: amit.tiwari@utoledo.edu.

PMID: 26003731
DOI: 10.1016/j.bbrc.2015.05.041

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.

Keywords: Cancer therapeutics; PI3K/AKT; PRAS40; mTORC1.

Publication types

Review

MeSH terms

Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism*
Animals
Carcinogenesis / drug effects
Carcinogenesis / genetics
Carcinogenesis / metabolism*
Drug Discovery
Gene Expression Regulation, Neoplastic
Humans
Molecular Targeted Therapy
Neoplasms / drug therapy
Neoplasms / genetics
Neoplasms / metabolism*
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism*
Signal Transduction*
TOR Serine-Threonine Kinases / metabolism*

Substances

AKT1S1 protein, human
Adaptor Proteins, Signal Transducing
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases