Mini-reviewTranslational control: A target for cancer therapy
Section snippets
Background
An important level of control of gene expression in eukaryotes occurs at the level of cap-mediated mRNA translation. Regulation of translation is critical for the accurate expression of a broad variety of genes that function in critical processes such as cell cycle progression and differentiation, as well as adaptation to cellular stress [1], [2], [3], [4]. Deregulation at this step is associated with aberrant gene expression leading to altered cell growth and possibly cancer. Translational
Breast cancer
A number of studies have looked at the role of eIF-4E in breast cancer outcome. eIF-4E was observed to be elevated 3- to 30-fold in breast cancer compared with benign breast tissue from non-cancer patients [27], [28], [29]. Increased eIF-4E has been observed in about 50% of ductal carcinoma in situ biopsies [25]. Li et al. analyzed eIF-4E expression in relation to disease parameters and revealed that high eIF-4E over-expression (defined as 7-fold elevation compared with benign breast tissue)
Discussion
eIF-4E plays a critical role in the regulation of cap-dependent protein translation and thus its activity is integral in determining global translation rate. The contribution of eIF-4E to malignant transformation and progression has been extensively elucidated over the past decade. It has been demonstrated in malignant tumors of the breast, head & neck, colon, prostate, bladder, cervix and lung, and has been related to tumorigenesis and disease progression. Ruggero et al. demonstrated that
Conclusions
Translation control has now been recognized as a crucial mechanism to regulate the expression of major regulatory genes involved in cellular functioning, cell cycle progression and differentiation. Further research on translational control and its therapeutic appliance has become increasingly important. However, to date only a limited number of therapeutic drugs are known to affect translational control. Some drugs such as antisense compounds and mTOR inhibitors are being tested in clinical
References (76)
Gene-specific regulation by general translation factors
Cell
(2002)- et al.
Ribosome loading onto the mRNA cap is driven by conformational coupling between eIF4G and eIF4E
Cell
(2003) - et al.
Mechanism of action and regulation of protein synthesis initiation factor 4E: effects of mRNA discrimination, cellular growth rate, and oncogenesis
Prog. Nucl. Acid Res. Mol. Biol.
(1993) - et al.
Eukaryotic translation initiation factor 4E regulates expression of cyclin D at transcriptional and posttranscriptional levels
J. Biol. Chem.
(1995) - et al.
Atypical adenomatous hyperplasia of the lung: a probable forerunner in the development of adenocarcinoma of the lung
Mod. Pathol.
(2001) - et al.
Expression of the eukaryotic translation initiation factors 4E and 2alpha in non-Hodgkin’s lymphomas
Am. J. Pathol.
(1999) - et al.
eIF-4E expression is associated with histopathologic grades in cervical neoplasia
Hum. Pathol.
(2005) - et al.
Tumor angiogenesis correlates with lymph node metastases in invasive bladder cancer
J. Urol.
(1995) - et al.
Regulation of eIF-4E BP1 phosphorylation by mTOR
J. Biol. Chem.
(1997) - et al.
Targeting mTOR signaling for cancer therapy
Curr. Opin. Pharmacol.
(2003)
Will mTOR inhibitors make it as cancer drugs?
Cancer Cell
Rapamycin is an effective inhibitor of human renal cancer metastasis
Kidney Int.
Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G
Cell
Translational control of protein synthesis
Annu. Rev. Biochem.
Pathway and mechanism of initiation of protein synthesis
Essentials of signal transduction
eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation
Annu. Rev. Biochem.
eIF4E-from translation to transformation
Oncogene
Translational control of malignancy: the mRNA cap-binding protein, eIF-4E, as a central regulator of tumor formation, growth, invasion and metastasis
Anticancer Res.
Regulation of translation initiation by FRAP/mTOR
Genes Dev.
eIF-4E expression and its role in malignancies and metastases
Oncogene
mRNAs containing extensive secondary structure in their 5′ noncoding region translate efficiently in cells over expressing initiation factor eIF-4E
EMBO J.
Translational regulation of vascular permeability factor by eukaryotic initiation factor 4E: implications for tumor angiogenesis
Int. J. Cancer
Translational enhancement of FGF-2 by eIF-4 factors, and alternate utilization of CUG and AUG codons for translation initiation
Oncogene
The role of c-myc in regulation of translation initiation
Oncogene
Elevated levels of cyclin D1 in response to increased expression of eukaryotic initiation factor 4E
Mol. Cell Biol.
Translation initiation of ornithine decarboxylase and nucleocytoplasmic transport of cyclin D1 mRNA are increased in cells overexpressing eukaryotic initiation factor 4E
Proc. Natl. Acad. Sci. USA
The emerging role for the mRNA cap-binding protein, eIF-4E, in metastatic progression
Translational control and metastatic progression: enhanced activity of the mRNA cap-binding protein eIF-4E selectively enhances translation of metastasis-related mRNAs
Clin. Exp. Metastasis
Regulation of 4EBP1 phosphorylation: a novel two-step mechanism
Genes Dev.
Hierarchical phosphorylation of the translation inhibitor 4E-BP1
Genes Dev.
4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the Akt (PKB) signaling pathway
Genes Dev.
Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR
Proc. Natl. Acad. Sci. USA
Elevated expression of eIF-4E in confined early breast cancer lesions: possible role of hypoxia
Int. J. Cancer
Over expression of hypoxia-inducible factor 1alpha in common human cancers and their metastases
Cancer Res.
Int. J. Cancer
Overexpression of eukaryotic initiation factor 4E (eIF4E) in breast carcinoma
Cancer
Differential expression of vascular endothelial growth factor mRNA vs. protein isoform expression in human breast cancer and relationship to elF-4E
Br. J. Cancer
Cited by (41)
Prospective pharmacological potential of cryptotanshinone in cancer therapy
2023, Pharmacological Research - Modern Chinese MedicineRNA-binding proteins in cancer drug discovery
2023, Drug Discovery TodayLong non-coding RNA EVADR induced by Fusobacterium nucleatum infection promotes colorectal cancer metastasis
2022, Cell ReportsCitation Excerpt :The detection of transcription factors by western blotting and polysome profiling has demonstrated that F. nucleatum can promote translation of Snail, Slug, and Zeb1 mRNAs by upregulating EVADR. Translational regulation is a frequent feature of tumorigenesis and is known to be involved in cancer metastasis (Silvera et al., 2010; Thumma and Kratzke, 2007). lncRNAs play a crucial role in regulating the translational efficiency of mRNAs.
The Eukaryotic Translation Initiation Factor 4E (eIF4E) as a Therapeutic Target for Cancer
2015, Advances in Protein Chemistry and Structural BiologyEIF4E-Overexpression imparts perillyl alcohol and rapamycin-mediated regulation of telomerase reverse transcriptase
2013, Experimental Cell ResearchHypoxia-inducible factor-1α (HIF-1α) promotes cap-dependent translation of selective mRNAs through up-regulating initiation factor eIF4E1 in breast cancer cells under hypoxia conditions
2013, Journal of Biological ChemistryCitation Excerpt :The recruitment of eIF4E1 to eIF4G1 is the key interaction in the eIF4F complex assembly (25, 26). Increased eIF4E1 levels and/or activity have been demonstrated in breast (27, 28), head and neck, colorectal, lung, ovarian (29, 30), prostate (31), bladder (32), brain (33), esophageal (34), and skin and cervical cancers (28, 35) as well as lymphomas (8, 36). The human eIF4E family consists of three members: eIF4E1, eIF4E2 (4EHP; 4E-LP), and eIF4E3 (37, 38).