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Post-transcriptional regulation in cancer progression

Microenvironmental control of alternative splicing and translation

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Journal of Cell Communication and Signaling Aims and scope

Abstract

The microenvironment acts as a conduit for cellular communication, delivering signals that direct development and sustain tissue homeostasis. In pathologies such as cancer, this integral function of the microenvironment is hijacked to support tumor growth and progression. Cells sense the microenvironment via signal transduction pathways culminating in altered gene expression. In addition to induced transcriptional changes, the microenvironment exerts its effect on the cell through regulation of post-transcriptional processes including alternative splicing and translational control. Here we describe how alternative splicing and protein translation are controlled by microenvironmental parameters such as oxygen availability. We also emphasize how these pathways can be utilized to support processes that are hallmarks of cancer such as angiogenesis, proliferation, and cell migration. We stress that cancer cells respond to their microenvironment through an integrated regulation of gene expression at multiple levels that collectively contribute to disease progression.

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  1. Department of Anatomy & Cell Biology, The Schulich School of Medicine and Dentistry, Western University, 438 Medical Science Building, London, ON, N6A 5C1, Canada

    Michael Jewer, Scott D. Findlay & Lynne-Marie Postovit

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  1. Michael Jewer
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  2. Scott D. Findlay
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  3. Lynne-Marie Postovit
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Correspondence to Lynne-Marie Postovit.

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Summary

Classically, the influence of the tumor microenvironment on the regulation of cellular phenotype has been assessed principally in terms of changes in gene expression at the level of transcription. Here, we detail evidence of an integrated response that also involves control of alternative splicing and protein translation, collectively contributing to tumor progression.

Michael Jewer and Scott D. Findlay are co-first authors.

Michael Jewer, Scott D Findlay, and Lynne-Marie Postovit all agree to submit this article to the Journal of Cell Communication and Signaling.

This work was supported by the Canadian Institutes for Health Research (MOP 89714, MOP 119589, and PLS 95381) and the Cancer Research Society to L.-M. Postovit. S.D. Findlay is the recipient of a scholarship from the Natural Sciences and Engineering Research Council of Canada (NSERC). M. Jewer is the recipient of a Canadian Institutes of Health Research (CIHR) scholarship. L.-M. Postovit is the recipient of the Premier New Investigator Award from the CIHR.

The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsors.

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Jewer, M., Findlay, S.D. & Postovit, LM. Post-transcriptional regulation in cancer progression. J. Cell Commun. Signal. 6, 233–248 (2012). https://doi.org/10.1007/s12079-012-0179-x

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  • DOI: https://doi.org/10.1007/s12079-012-0179-x

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