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Int J Clin Exp Pathol 2011;4(5):476-495

Review Ariticle
Mammalian target of rapamycin: a central node of complex signaling cascades

Yoh Dobashi, Yasutaka Watanabe, Chihiro Miwa, Sakae Suzuki, Shinichiro Koyama

Department of Pathology, Respiratory Medicine and Phamacy Saitama Medical Center, Jichi Medical University, Saitama, Japan

Received June 7, 2011; accepted June 13, 2011; Epub June 15, 2011, published June 20, 2011

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.(IJCEP1106002)

Keywords: mTOR, rapamycin, lung cancer, molecular targeting therapy

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Address all correspondence to:
Yoh Dobashi, MD, PhD
Department of Pathology
Saitama Medical Center, Jichi Medical University
1-847 Amanuma, Omiya, Saitama
Saitama  330-8503  Japan.
Tel/Fax: 81-48-640-4018
E-mail:
ydobashi@omiya.jichi.ac.jp