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, Professor Alison |
| Authors: | Holroyd, A. K., and Michie, A. M. |
| College/School: | College of Medical Veterinary and Life Sciences > School 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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