ArticleMolecular cancer research : MCR2014
Mcl-1 mediates TWEAK/Fn14-induced non-small cell lung cancer survival and therapeutic response.
Article in Molecular cancer research : MCR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- A Transcriptomic Analysis of Cancer-Stromal Interactome in Lung Cancer Xenograft Models.Cancer science · 2026Article
- Optimizing Membrane Composition With C15 and Choline: A Novel Hypothesis to Mitigate Cancer Risk.Cureus · 2025Review
- High expression of the cachexia-related protein Fn14 in esophageal squamous cell carcinoma correlates with poor chemotherapy response and anti-Fn14 therapy decreases chemotherapeutic resistance.British journal of cancer · 2025Article
- ElevatedJournal of thoracic disease · 2024Article
- Single-cell and Bulk RNA-Seq reveal angiogenic heterogeneity and microenvironmental features to evaluate prognosis and therapeutic response in lung adenocarcinoma.Frontiers in immunology · 2024Article
- TWEAK-Fn14-RelB Signaling Cascade Promotes Stem Cell-like Features that Contribute to Post-Chemotherapy Ovarian Cancer Relapse.Molecular cancer research : MCR · 2023Article
- Lower Expression of TWEAK is Associated with Poor Survival and Dysregulate TIICs in Lung Adenocarcinoma.Disease markers · 2022Article
- Evaluation of Computationally Designed Peptides against TWEAK, a Cytokine of the Tumour Necrosis Factor Ligand Family.International journal of molecular sciences · 2021Article
- Myeloid cell leukemia-1 is an important predictor of survival and progression of small cell lung cancer.Annals of translational medicine · 2020Article
- NCAPH is negatively associated with Mcl‑1 in non‑small cell lung cancer.Molecular medicine reports · 2020Article
- Therapeutic efficacy and safety of a human fusion construct targeting the TWEAK receptor Fn14 and containing a modified granzyme B.Journal for immunotherapy of cancer · 2020Article
- Formononetin inhibits tumor growth by suppression of EGFR-Akt-Mcl-1 axis in non-small cell lung cancer.Journal of experimental & clinical cancer research : CR · 2020Article
- Deguelin suppresses non-small cell lung cancer by inhibiting EGFR signaling and promoting GSK3β/FBW7-mediated Mcl-1 destabilization.Cell death & disease · 2020Article
- TNFRSF12A and CD38 Contribute to a Vicious Circle for Chronic Obstructive Pulmonary Disease by Engaging Senescence Pathways.Frontiers in cell and developmental biology · 2020Article
- LncRNA TUG1 contributes to ESCC progression via regulating miR-148a-3p/MCL-1/Wnt/β-catenin axis in vitro.Thoracic cancer · 2020Article
- Elevated expression of mcl-1 inhibits apoptosis and predicts poor prognosis in patients with surgically resected non-small cell lung cancer.Diagnostic pathology · 2019Article
- Article
- Binding of eEF1A2 to the RNA-dependent protein kinase PKR modulates its activity and promotes tumour cell survival.British journal of cancer · 2018Article
- Src Promotes Metastasis of Human Non-Small Cell Lung Cancer Cells through Fn14-Mediated NF-κB Signaling.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Vorinostat and metformin sensitize EGFR-TKI resistant NSCLC cells via BIM-dependent apoptosis induction.Oncotarget · 2017Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
unlabelledInsensitivity to standard clinical interventions, including chemotherapy, radiotherapy, and tyrosine kinase inhibitor (TKI) treatment, remains a substantial hindrance towards improving the prognosis of patients with non-small cell lung cancer (NSCLC). The molecular mechanism of therapeutic resistance remains poorly understood. The TNF-like weak inducer of apoptosis (TWEAK)-FGF-inducible 14 (TNFRSF12A/Fn14) signaling axis is known to promote cancer cell survival via NF-κB activation and the upregulation of prosurvival Bcl-2 family members. Here, a role was determined for TWEAK-Fn14 prosurvival signaling in NSCLC through the upregulation of myeloid cell leukemia sequence 1 (MCL1/Mcl-1). Mcl-1 expression significantly correlated with Fn14 expression, advanced NSCLC tumor stage, and poor patient prognosis in human primary NSCLC tumors. TWEAK stimulation of NSCLC cells induced NF-κB-dependent Mcl-1 protein expression and conferred Mcl-1-dependent chemo- and radioresistance. Depletion of Mcl-1 via siRNA or pharmacologic inhibition of Mcl-1, using EU-5148, sensitized TWEAK-treated NSCLC cells to cisplatin- or radiation-mediated inhibition of cell survival. Moreover, EU-5148 inhibited cell survival across a panel of NSCLC cell lines. In contrast, inhibition of Bcl-2/Bcl-xL function had minimal effect on suppressing TWEAK-induced cell survival. Collectively, these results position TWEAK-Fn14 signaling through Mcl-1 as a significant mechanism for NSCLC tumor cell survival and open new therapeutic avenues to abrogate the high mortality rate seen in NSCLC. IMPLICATIONS: The TWEAK-Fn14 signaling axis enhances lung cancer cell survival and therapeutic resistance through Mcl-1, positioning both TWEAK-Fn14 and Mcl-1 as therapeutic opportunities in lung cancer.
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