ArticleMolecular cancer therapeutics2008
Akt-mediated eminent expression of c-FLIP and Mcl-1 confers acquired resistance to TRAIL-induced cytotoxicity to lung cancer cells.
Article in Molecular cancer therapeutics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 92 citations in OpenAlex.
- Article
- Bcl-xL inhibition radiosensitizesCancer research communications · 2022Article
- Epigenetic Deregulation of Apoptosis in Cancers.Cancers · 2021Review
- Colicin N Mediates Apoptosis and Suppresses Integrin-Modulated Survival in Human Lung Cancer Cells.Molecules (Basel, Switzerland) · 2020Article
- Epigenetic Regulation of RIP3 Suppresses Necroptosis and Increases Resistance to Chemotherapy in NonSmall Cell Lung Cancer.Translational oncology · 2020Article
- Accelerated degradation of cFLIPScientific reports · 2019Article
- Wentilactone A induces cell apoptosis by targeting AKR1C1 gene via the IGF-1R/IRS1/PI3K/AKT/Nrf2/FLIP/Caspase-3 signaling pathway in small cell lung cancer.Oncology letters · 2018Article
- Development of acquired resistance to lapatinib may sensitise HER2-positive breast cancer cells to apoptosis induction by obatoclax and TRAIL.BMC cancer · 2018Article
- Peptides extracted from edible mushroom: Lentinus squarrosulus induces apoptosis in human lung cancer cells.Pharmaceutical biology · 2017Article
- Article
- Article
- Polyphenols from Korean prostrate spurge Euphorbia supina induce apoptosis through the Fas-associated extrinsic pathway and activation of ERK in human leukemic U937 cells.Oncology reports · 2016Article
- Autophagy-Mediated Degradation of IAPs and c-FLIP(L) Potentiates Apoptosis Induced by Combination of TRAIL and Chal-24.Journal of cellular biochemistry · 2016Article
- The Deubiquitinase Inhibitor PR-619 Sensitizes Normal Human Fibroblasts to Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL)-mediated Cell Death.The Journal of biological chemistry · 2016Article
- Marine Drugs Regulating Apoptosis Induced by Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL).Marine drugs · 2015Review
- A set of NF-κB-regulated microRNAs induces acquired TRAIL resistance in lung cancer.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Carbon nanotubes induce apoptosis resistance of human lung epithelial cells through FLICE-inhibitory protein.Toxicological sciences : an official journal of the Society of Toxicology · 2015Article
- A signaling pathway consisting of miR-551b, catalase and MUC1 contributes to acquired apoptosis resistance and chemoresistance.Carcinogenesis · 2014Article
- A JNK-mediated autophagy pathway that triggers c-IAP degradation and necroptosis for anticancer chemotherapy.Oncogene · 2014Article
- TRAIL combinations: The new 'trail' for cancer therapy (Review).Oncology letters · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anticancer agent due to its selectivity in killing transformed cells. However, TRAIL can also stimulate the proliferation and metastasis of TRAIL-resistant cancer cells. Thus, acquired TRAIL resistance during TRAIL therapy would shift the patient's treatment from beneficial to detrimental. In this study, we focused on the acquired TRAIL resistance mechanism and showed that the elevated expression of the antiapoptotic factor cellular FLICE-like inhibitory protein (c-FLIP) and the prosurvival Bcl-2 family member myeloid cell leukemia-1 (Mcl-1) underlie the main mechanism of this type of TRAIL resistance in lung cancer cells. Chronic exposure to TRAIL resulted in lung cancer cell resistance to TRAIL-induced cytotoxicity, and this resistance was associated with the increase in the cellular levels of c-FLIP(L) and Mcl-1(L). Overexpresssion of c-FLIP(L) suppressed recruitment of caspase-8 to the death-inducing signaling complex, whereas increased Mcl-1(L) expression blunted the mitochondrial apoptosis pathway. The elevation of c-FLIP(L) and Mcl-1(L) expression was due to Akt-mediated stabilization of these proteins in TRAIL-resistant cells. Importantly, suppressing c-FLIP(L) and Mcl-1(L) expression by RNA interference collectively alleviated acquired TRAIL resistance. Taken together, these results identify c-FLIP(L) and Mcl-1(L) as the major determinants of acquired TRAIL resistance and could be molecular targets for improving the therapeutic value of TRAIL against lung cancer.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.