ArticleOncotarget2016
eIF4B is a convergent target and critical effector of oncogenic Pim and PI3K/Akt/mTOR signaling pathways in Abl transformants.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Curcumin analog GO-Y030 inhibits tumor metastasis and glycolysis.Journal of biochemistry · 2023Article
- Complex CDKL5 translational regulation and its potential role in CDKL5 deficiency disorder.Frontiers in cellular neuroscience · 2023Article
- Phosphoproteomics of primary AML patient samples reveals rationale for AKT combination therapy and p53 context to overcome selinexor resistance.Cell reports · 2022Article
- PARK2 regulates eIF4B-driven lymphomagenesis.Molecular cancer research : MCR · 2022Article
- A Review: PI3K/AKT/mTOR Signaling Pathway and Its Regulated Eukaryotic Translation Initiation Factors May Be a Potential Therapeutic Target in Esophageal Squamous Cell Carcinoma.Frontiers in oncology · 2022Review
- Co-Targeting PIM Kinase and PI3K/mTOR in NSCLC.Cancers · 2021Article
- OTS167 blocks FLT3 translation and synergizes with FLT3 inhibitors in FLT3 mutant acute myeloid leukemia.Blood cancer journal · 2021Article
- Deficiency of eIF4B Increases Mouse Mortality and Impairs Antiviral Immunity.Frontiers in immunology · 2021Article
- Therapeutic Potential of PI3K/AKT/mTOR Pathway in Gastrointestinal Stromal Tumors: Rationale and Progress.Cancers · 2020Review
- Broad-spectrum antitumor properties of Withaferin A: a proteomic perspective.RSC medicinal chemistry · 2020Review
- PIM Kinases and Their Relevance to the PI3K/AKT/mTOR Pathway in the Regulation of Ovarian Cancer.Biomolecules · 2018Review
- Article
- The Roles of microRNAs in Regulating the Expression of PD-1/PD-L1 Immune Checkpoint.International journal of molecular sciences · 2017Review
- Understanding of leukemic stem cells and their clinical implications.Molecular cancer · 2017Review
- Hypoxic 3D in vitro culture models reveal distinct resistance processes to TKIs in renal cancer cells.Cell & bioscience · 2017Article
- miR-150 exerts antileukemia activity in vitro and in vivo through regulating genes in multiple pathways.Cell death & disease · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of eIF4B correlates with Abl-mediated cellular transformation, but the precise mechanisms are largely unknown. Here we show that eIF4B is a convergent substrate of JAK/STAT/Pim and PI3K/Akt/mTOR pathways in Abl transformants. Both pathways phosphorylated eIF4B in Abl-transformed cells, and such redundant regulation was responsible for the limited effect of single inhibitor on Abl oncogenicity. Persistent inhibition of one signaling pathway induced the activation of the other pathway and thereby restored the phosphorylation levels of eIF4B. Simultaneous inhibition of the two pathways impaired eIF4B phosphorylation more effectively, and synergistically induced apoptosis in Abl transformed cells and inhibited the growth of engrafted tumors in nude mice. Similarly, the survival of Abl transformants exhibited a higher sensitivity to the pharmacological inhibition, when combined with the shRNA-based silence of the other pathway. Interestingly, such synergy was dependent on the phosphorylation status of eIF4B on Ser422, as overexpression of eIF4B phosphomimetic mutant S422E in the transformants greatly attenuated the synergistic effects of these inhibitors on Abl oncogenicity. In contrast, eIF4B knockdown sensitized Abl transformants to undergo apoptosis induced by the combined blockage. Collectively, the results indicate that eIF4B integrates the signals from Pim and PI3K/Akt/mTOR pathways in Abl-expressing leukemic cells, and is a promising therapeutic target for such cancers.
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