The role of mTOR-mediated signaling in the regulation of cellular migration

Holroyd, A. K. and Michie, A. M. (2018) The role of mTOR-mediated signaling in the regulation of cellular migration. Immunology Letters, 196, pp. 74-79. (doi:10.1016/j.imlet.2018.01.015) (PMID:29408410)

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Abstract

Mechanistic target for rapamycin (mTOR) is a serine/threonine protein kinase that forms two distinct complexes mTORC1 and mTORC2, integrating mitogen and nutrient signals to regulate cell survival and proliferation; processes which are commonly deregulated in human cancers. mTORC1 and mTORC2 have divergent molecular associations and cellular functions: mTORC1 regulates in mRNA translation and protein synthesis, while mTORC2 is involved in the regulation of cellular survival and metabolism. Through AKT phosphorylation/activation, mTORC2 has also been reported to regulate cell migration. Recent attention has focused on the aberrant activation of the PI3K/mTOR pathway in B cell malignancies and there is growing evidence for its involvement in disease pathogenesis, due to its location downstream of other established novel drug targets that intercept B cell receptor (BCR) signals. Shared pharmacological features of BCR signal inhibitors include a striking “lymphocyte redistribution” effect whereby patients experience a sharp increase in lymphocyte count on initiation of therapy followed by a steady decline. Chronic lymphocytic leukemia (CLL) serves as a paradigm for migration studies as lymphocytes are among the most widely travelled cells in the body, a product of their role in immunological surveillance. The subversion of normal lymphocyte movement in CLL is being elucidated; this review aims to describe the migration impairment which occurs as part of the wider context of cancer cell migration defects, with a focus on the role of mTOR in mediating migration effects downstream of BCR ligation and other microenvironmental signals.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Holroyd, Dr Ailsa and Michie, Dr Alison
Authors: Holroyd, A. K., and Michie, A. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Immunology Letters
Publisher:Elsevier
ISSN:0165-2478
ISSN (Online):1879-0542
Published Online:03 February 2018
Copyright Holders:Copyright © 2018 2018 European Federation of Immunological Societies.
First Published:First published in Immunology Letters 196:74-79
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
600561MICA: Determining the therapeutic potential of targeting mTORC-1/2 in chronic lymphocytic leukaemia - a pre-clinical studyAlison MichieMedical Research Council (MRC)MR/K014854/1ICS - PAUL O'GORMAN LEUKAEMIA RESEARCH C
698661Elucidating the role of individual mTor complexes in the development and progression of chronic lymphocytic leukaemiaAlison MichieBloodwise (BLOODWIS)15041ICS - PAUL O'GORMAN LEUKAEMIA RESEARCH C
653711Elucidating the role of mTor kinase signalling in chronic lymphocytic leukaemiaAilsa HolroydThe Kay Kendall Leukaemia Fund (KENDALL)KKL838RI CANCER SCIENCES