ArticleBMC cancer2015
Control of the MYC-eIF4E axis plus mTOR inhibitor treatment in small cell lung cancer.
Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- mRNA Network: Solution for Tracking Chemotherapy Insensitivity in Small-Cell Lung Cancer.Journal of healthcare engineering · 2021Trial
- mTOR in radiotherapy of lung cancer: Mechanisms of radiation resistance and therapeutic implications (Review).International journal of oncology · 2026Review
- c-Myc-dependent LAMP3 regulates the proliferation, metastasis and metabolic reprogramming of tongue squamous cell carcinoma.Scientific reports · 2025Article
- MYC is a clinically significant driver of mTOR inhibitor resistance in breast cancer.The Journal of experimental medicine · 2023Article
- [Study on the Biological Function of Abemecilib in Inhibiting the Proliferation, Invasion and Migration of Small Cell Lung Cancer with High c-Myc Expression].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2023Article
- Inhibitors of ABCB1 and ABCG2 overcame resistance to topoisomerase inhibitors in small cell lung cancer.Thoracic cancer · 2022Article
- CTP sensing and Mec1ATR-Rad53CHK1/CHK2 mediate a two-layered response to inhibition of glutamine metabolism.PLoS genetics · 2022Article
- A low-molecular-weight compound exerts anticancer activity against breast and lung cancers by disrupting EGFR/Eps8 complex formation.Journal of experimental & clinical cancer research : CR · 2019Article
- Alisol B 23-acetate-induced HepG2 hepatoma cell death through mTOR signaling-initiated GChinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2019Article
- Knockdown of ribosomal protein S15A inhibits human kidney cancer cell growth in vitro and in vivo.Molecular medicine reports · 2019Article
- eIF4E Phosphorylation in Prostate Cancer.Neoplasia (New York, N.Y.) · 2018Review
- EPHA3 regulates the multidrug resistance of small cell lung cancer via the PI3K/BMX/STAT3 signaling pathway.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Targeted drugs in small-cell lung cancer.Translational lung cancer research · 2016Review
- Insights into Novel Prognostic and Possible Predictive Biomarkers of Lung Neuroendocrine Tumors.Cancer genomics & proteomicsReview
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMammalian target of rapamycin (mTOR) inhibitors have anti-tumor effects against renal cell carcinoma, pancreatic neuroendocrine cancer and breast cancer. In this study, we analyzed the antitumor effects of mTOR inhibitors in small cell lung cancer (SCLC) cells and sought to clarify the mechanism of resistance to mTOR inhibitors.
methodsWe analyzed the antitumor effects of three mTOR inhibitors including everolimus in 7 SCLC cell lines by MTS assay. Gene-chip analysis, receptor tyrosine kinases (RTK) array and Western blotting analysis were performed to identify molecules associated with resistance to everolimus.
resultsOnly SBC5 cells showed sensitivity to everolimus by MTS assay. We established two everolimus resistant-SBC5 cell lines (SBC5 R1 and SBC5 R10) by continuous exposure to increasing concentrations of everolimus stepwise. SPP1 and MYC were overexpressed in both SBC5 R1 and SBC5 R10 by gene-chip analysis. High expression levels of eukaryotic translation initiation factor 4E (eIF4E) were observed in 5 everolimus-resistant SCLC cells and SBC5 R10 cells by Western blotting. MYC siRNA reduced eIF4E phosphorylation in SBC5 cells, suggesting that MYC directly activates eIF4E by an mTOR-independent bypass pathway. Importantly, after reduction of MYC or eIF4E by siRNAs, the SBC5 parent and two SBC5-resistant cells displayed increased sensitivity to everolimus relative to the siRNA controls.
conclusionThese findings suggest that eIF4E has been shown to be an important factor in the resistance to everolimus in SCLC cells. Furthermore, a link between MYC and mTOR-independent eIF4E contribute to the resistance to everolimus in SCLC cells. Control of the MYC-eIF4E axis may be a novel therapeutic strategy for everolimus action in SCLC.
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