Suppression of oncogenic protein translation via targeting eukaryotic translation initiation factor 4E overcomes chemo-resistance in nasopharyngeal carcinoma

Xu, Mingfang; Tao, Zezhang; Wang, Shuai; Jiang, Yidao; Qu, Mei

doi:10.1016/j.bbrc.2019.03.118

Cited by 8 publications

(7 citation statements)

References 30 publications

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“…Thus, it appears that either purine or pyrimidine NTPs can become limiting for rRNA transcription. This has important implications for combination therapy strategies as hyperactive protein translation is a known mechanism of resistance to chemotherapy agents such as cisplatin 66 and paclitaxel 67 .…”

Section: Effects Of Inhibiting (D)ntp Synthesis On Growth and Prolife...mentioning

confidence: 99%

Nucleotide metabolism: a pan-cancer metabolic dependency

Mullen

Singh

2023

Nat Rev Cancer

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Metabolic alterations are a key hallmark of cancer cells, and the augmented synthesis and use of nucleotide triphosphates is a critical and universal metabolic dependency of cancer cells across different cancer types and genetic backgrounds. Many of the aggressive behaviours of cancer cells, including uncontrolled proliferation, chemotherapy resistance, immune evasion and metastasis, rely heavily on augmented nucleotide metabolism. Furthermore, most of the known oncogenic drivers upregulate nucleotide biosynthetic capacity, suggesting that this phenotype is a prerequisite for cancer initiation and progression. Despite the wealth of data demonstrating the efficacy of nucleotide synthesis inhibitors in preclinical cancer models and the well-established clinical use of these drugs in certain cancer settings, the full potential of these agents remains unrealized. In this Review, we discuss recent studies that have generated mechanistic insights into the diverse biological roles of hyperactive cancer cell nucleotide metabolism. We explore opportunities for combination therapies that are highlighted by these recent advances and detail key questions that remain to be answered, with the goal of informing urgently warranted future studies.

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Section: Effects Of Inhibiting (D)ntp Synthesis On Growth and Prolife...mentioning

confidence: 99%

Nucleotide metabolism: a pan-cancer metabolic dependency

Mullen

Singh

2023

Nat Rev Cancer

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“…By making the use of NPC xenograft mouse models, the authors demonstrate that Ribavirin markedly enhances the efficacy of cisplatin in vivo without generating substantial toxicity in mice. 85 Emerging data have evaluated the ability of a large variety of nucleotide and nucleoside analogs of 7-Methyl GTP for inhibiting binding of eIF4E to capped mRNA specifically. Similarly, 4EGI-1, a small-molecule inhibitor that mimics 4E-BP1 has shown efficacious antitumor activity by abrogating eIF4E-eIF4G interaction.…”

Section: Strategies For Targeting Eif4ementioning

confidence: 99%

“…Recently, Ribavirin has been shown to phenocopy the effects of eIF4E knockdown in nasopharyngeal carcinoma. By making the use of NPC xenograft mouse models, the authors demonstrate that Ribavirin markedly enhances the efficacy of cisplatin in vivo without generating substantial toxicity in mice . Emerging data have evaluated the ability of a large variety of nucleotide and nucleoside analogs of 7‐Methyl GTP for inhibiting binding of eIF4E to capped mRNA specifically.…”

Section: Possible Therapeutic Strategies For Targeting Eif4ementioning

confidence: 99%

Eukaryotic initiation factor 4E (eIF4E): A recap of the cap‐binding protein

Batool

Aashaq

Andrabi

2019

J of Cellular Biochemistry

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Eukaryotic initiation factor 4E (eIF4E), a fundamental effector and rate limiting element of protein synthesis, binds the 7‐methylguanosine cap at the 5′ end of eukaryotic messenger RNA (mRNA) specifically as a constituent of eIF4F translation initiation complex thus facilitating the recruitment of mRNA to the ribosomes. This review focusses on the engagement of signals contributing to growth factor originated maxim and their role in the activation of eIF4E to achieve a collective influence on cellular growth, with a key focus on conjuring vital processes like protein synthesis. The review invites considerable interest in elevating the appeal of eIF4E beyond its role in regulating translation viz a viz cancer genesis, attributed to its phosphorylation state that improves the prospect for the growth of the cancerous cell. This review highlights the latest studies that have envisioned to target these pathways and ultimately the translational machinery for therapeutic intervention. The review also brings forward the prospect of eIF4E to act as a converging juncture for signaling pathways like mTOR/PI3K and Mnk/MAPK to promote tumorigenesis.

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“…The use of mitochondrial genes as prognostic factors is likely to apply to CRC patients at all phases, from the early stage to the late stage, to the stage of metastasis. We know that the amounts of mRNA and protein of a gene are associated with many factors, including mRNA modification [ 28 , 29 ], translation efficiency [ 30 , 31 ], and protein stability and degradation [ 32 , 33 ]. A change in the expression of a gene on mRNA may not result in a difference in the protein level that would affect the body's physiological activities.…”

Section: Discussionmentioning

confidence: 99%

Multi-omics analyses of human colorectal cancer revealed three mitochondrial genes potentially associated with poor outcomes of patients

et al. 2021

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Background The identification of novel functional biomarkers is essential for recognizing high-risk patients, predicting recurrence, and searching for appropriate treatment. However, no prognostic biomarker has been applied for colorectal cancer (CRC) in the clinic. Methods Integrated with transcriptomic data from public databases, multi-omics examinations were conducted to search prognostic biomarkers for CRC. Moreover, the potential biological functions and regulatory mechanism of these predictive genes were also explored. Results In this study, we revealed that three mitochondrial genes were associated with the poor prognosis of CRC. Integrated analyses of transcriptome and proteome of CRC patients disclosed numerous down-regulated mitochondrial genes at both mRNA and protein levels, suggesting a vital role of mitochondria in carcinogenesis. Combined with the bioinformatics studies of transcriptomic datasets of 538 CRC patients, three mitochondrial prognostic genes were eventually selected out, including HIGD1A, SUCLG2, and SLC25A24. The expression of HIGD1A exhibited a significant reduction in two subtypes of adenoma and six subtypes of CRC, while the down-regulation of SUCLG2 and SLC25A24 showed more advantages in rectal mucinous adenocarcinoma. Moreover, we unveiled that these three genes had common expressions and might collaboratively participate in the synthesis of ribosomes. Our original multi-omics datasets, including DNA methylation, structural variants, chromatin accessibility, and phosphoproteome, further depicted the altered modifications on their potential transcriptional factors. Conclusions In summary, HIGD1A, SUCLG2, and SLC25A24 might serve as predictive biomarkers for CRC. The biological activities they involved in and their upstream regulators we uncovered would provide a functional context for the further-in-depth mechanism study. Graphic abstract

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Suppression of oncogenic protein translation via targeting eukaryotic translation initiation factor 4E overcomes chemo-resistance in nasopharyngeal carcinoma

Cited by 8 publications

References 30 publications

Nucleotide metabolism: a pan-cancer metabolic dependency

Nucleotide metabolism: a pan-cancer metabolic dependency

Eukaryotic initiation factor 4E (eIF4E): A recap of the cap‐binding protein

Multi-omics analyses of human colorectal cancer revealed three mitochondrial genes potentially associated with poor outcomes of patients

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