2013
DOI: 10.1038/onc.2013.153
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Translation factors and ribosomal proteins control tumor onset and progression: how?

Abstract: Gene expression is shaped by translational control. The modalities and the extent by which translation factors modify gene expression have revealed therapeutic scenarios. For instance, eukaryotic initiation factor (eIF)4E activity is controlled by the signaling cascade of growth factors, and drives tumorigenesis by favoring the translation of specific mRNAs. Highly specific drugs target the activity of eIF4E. Indeed, the antitumor action of mTOR complex 1 (mTORc1) blockers like rapamycin relies on their capabi… Show more

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Cited by 76 publications
(81 citation statements)
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“…Translation is a major downstream target of mTOR and is a highly regulated process that is often overactive in cancer. [12,13] Once activated, mTOR phosphorylates two effector proteins, P70S6K and 4E-BP1. [14,15] P70S6K controls the phosphorylation of eIF4B, a protein involved in eIF4A helicase efficiency, whereas, 4E-BP1 is a well-studied protein in the control of eIF4E, the rate limiting translation initiation factor.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…Translation is a major downstream target of mTOR and is a highly regulated process that is often overactive in cancer. [12,13] Once activated, mTOR phosphorylates two effector proteins, P70S6K and 4E-BP1. [14,15] P70S6K controls the phosphorylation of eIF4B, a protein involved in eIF4A helicase efficiency, whereas, 4E-BP1 is a well-studied protein in the control of eIF4E, the rate limiting translation initiation factor.…”
Section: Resultsmentioning
confidence: 99%
“…[26] Most of the translation initiation factors have altered expression in different types of cancer [12] and ribosomal disorders are known to lead to increased cancer risk. [13,27] New research suggests that eIF4A is critically involved in BRAF and MEK inhibitor resistance in melanoma, colon, and thyroid cancer cell lines and eIF4F causes oncogenic translation. [28,29] It was previously discovered that the MAPK and mTOR/PI3K pathways converge on eIF4B [20] but to our knowledge this is the first evidence of EGFR and mTOR inhibitor synergy being regulated by eIF4B in TNBC.…”
Section: Discussionmentioning
confidence: 99%
“…Nevertheless, such compromise, if it exists, must be minimal, as these patients can be successfully vaccinated. Finally, it is also possible that partial loss of ribosome activity has differential effects on the translation of growth-supporting versus growth-suppressing proteins, as already shown for other modifications to the translational machinery (164, 165). …”
Section: R-proteins and Diseasementioning
confidence: 91%
“…This view was challenged in recent years by genetic evidence demonstrating that ribosomal alterations modulate tumorigenesis [34,66]. Enlargement of eIF6 containing nucleoli is a feature of aggressive colorectal tumors [59].…”
Section: Eif6 In Cancermentioning
confidence: 99%