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Translational Regulation of Cancer Metastasis

Douglas S. Micalizzi, Richard Y. Ebright, Daniel A. Haber and Shyamala Maheswaran
Douglas S. Micalizzi
1Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts.
2Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
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  • ORCID record for Douglas S. Micalizzi
Richard Y. Ebright
1Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts.
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Daniel A. Haber
1Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts.
2Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
3Howard Hughes Medical Institute, Chevy Chase, Maryland.
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  • For correspondence: maheswaran@helix.mgh.harvard.edu DHABER@mgh.harvard.edu
Shyamala Maheswaran
1Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts.
4Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts.
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  • For correspondence: maheswaran@helix.mgh.harvard.edu DHABER@mgh.harvard.edu
DOI: 10.1158/0008-5472.CAN-20-2720 Published February 2021
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Abstract

Deregulation of the mRNA translational process has been observed during tumorigenesis. However, recent findings have shown that deregulation of translation also contributes specifically to cancer cell spread. During metastasis, cancer cells undergo changes in cellular state, permitting the acquisition of features necessary for cell survival, dissemination, and outgrowth. In addition, metastatic cells respond to external cues, allowing for their persistence under significant cellular and microenvironmental stresses. Recent work has revealed the importance of mRNA translation to these dynamic changes, including regulation of cell states through epithelial-to-mesenchymal transition and tumor dormancy and as a response to external stresses such as hypoxia and immune surveillance. In this review, we focus on examples of altered translation underlying these phenotypic changes and responses to external cues and explore how they contribute to metastatic progression. We also highlight the therapeutic opportunities presented by aberrant mRNA translation, suggesting novel ways to target metastatic tumor cells.

Footnotes

  • Cancer Res 2021;81:517–24

  • Received August 9, 2020.
  • Revision received September 25, 2020.
  • Accepted October 23, 2020.
  • Published first January 21, 2021.
  • ©2021 American Association for Cancer Research.
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Cancer Research: 81 (3)
February 2021
Volume 81, Issue 3
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Translational Regulation of Cancer Metastasis
Douglas S. Micalizzi, Richard Y. Ebright, Daniel A. Haber and Shyamala Maheswaran
Cancer Res February 1 2021 (81) (3) 517-524; DOI: 10.1158/0008-5472.CAN-20-2720

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Translational Regulation of Cancer Metastasis
Douglas S. Micalizzi, Richard Y. Ebright, Daniel A. Haber and Shyamala Maheswaran
Cancer Res February 1 2021 (81) (3) 517-524; DOI: 10.1158/0008-5472.CAN-20-2720
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    • Abstract
    • Introduction
    • Translational Dysregulation
    • Translational Control of Cell States
    • Translational Deregulation by Tumor Microenvironmental Factors
    • Therapeutic Vulnerabilities Presented by Translational Deregulation in Cancer
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