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Translational control of aberrant stress responses as a hallmark of cancer
The Journal of pathology, 2018-04, Vol.244 (5), p.650-666
El‐Naggar, Amal M
Sorensen, Poul H
2018
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
El‐Naggar, Amal M
Sorensen, Poul H
Titel
Translational control of aberrant stress responses as a hallmark of cancer
Ist Teil von
The Journal of pathology, 2018-04, Vol.244 (5), p.650-666
Ort / Verlag
Chichester, UK: John Wiley & Sons, Ltd
Erscheinungsjahr
2018
Quelle
Access via Wiley Online Library
Beschreibungen/Notizen
Altered mRNA translational control is emerging as a critical factor in cancer development and progression. Targeting specific elements of the translational machinery, such as mTORC1 or eIF4E, is emerging as a new strategy for innovative cancer therapy. While translation of most mRNAs takes place through cap‐dependent mechanisms, a sub‐population of cellular mRNA species, particularly stress‐inducible mRNAs with highly structured 5'‐UTR regions, are primarily translated through cap‐independent mechanisms. Intriguingly, many of these mRNAs encode proteins that are involved in tumour cell adaptation to microenvironmental stress, and thus linked to aggressive behaviour including tumour invasion and metastasis. This necessitates a rigorous search for links between microenvironmental stress and aggressive tumour phenotypes. Under stress, cells block global protein synthesis to preserve energy while maintaining selective synthesis of proteins that support cell survival. One highly conserved mechanism to regulate protein synthesis under cell stress is to sequester mRNAs into cytosolic aggregates called stress granules (SGs), where their translation is silenced. SGs confer survival advantages and chemotherapeutic resistance to tumour cells under stress. Recently, it has been shown that genetically blocking SG formation dramatically reduces tumour invasive and metastatic capacity in vivo. Therefore, targeting SG formation might represent a potential treatment strategy to block cancer metastasis. Here, we present the critical link between selective mRNA translation, stress adaptation, SGs, and tumour progression. Further, we also explain how deciphering mechanisms of selective mRNA translation occurs under cell stress holds great promise for the identification of new targets in the treatment of cancer. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Sprache
Englisch
Identifikatoren
ISSN: 0022-3417
eISSN: 1096-9896
DOI: 10.1002/path.5030
Titel-ID: cdi_proquest_miscellaneous_1983847004
Format
–
Schlagworte
Adaptation
,
Blocking
,
Cancer
,
Cell survival
,
Cellular structure
,
Chemoresistance
,
Initiation factor eIF-4E
,
Invasiveness
,
Medical innovations
,
Metastases
,
Metastasis
,
microenvironmental stress
,
mRNA
,
Protein biosynthesis
,
Protein synthesis
,
Proteins
,
selective mRNA translation
,
Stress
,
stress granules
,
Therapeutic applications
,
Tumors
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