ArticleOncogene2018
C5a induces A549 cell proliferation of non-small cell lung cancer via GDF15 gene activation mediated by GCN5-dependent KLF5 acetylation.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Clinicopathological features and prognostic significance of C5aR in human solid tumors: a Meta-analysis.BMC cancer · 2021Pooled it
- Tumor-derived GDF15 induces CCN3⁺ Schwann cells to promote cancer pain in pancreatic cancer.Nature communications · 2026Article
- The Role of Complement Anaphylatoxins (C3a and C5a) in Non-small Cell Lung Cancer: A Systematic Review.Cureus · 2026Review
- Abnormal expression and potential clinical value of oncogenic Krüppel-like factor-5 in lung squamous cell carcinoma.World journal of clinical oncology · 2025Article
- KLF9 Inhibits Brain Metastasis of Non-Small Cell Lung Cancer by Regulating Ceramide Synthase 1 Synthesis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Jet lag-induced circadian disruption elevates glioma risk by altering molecular profiles in distinct brain regions.Discover oncology · 2025Article
- UPR-induced intracellular C5aR1 promotes adaptation to the hypoxic tumour microenvironment.Cell death & disease · 2025Article
- IL-17 triggers PD-L1 gene transcription in NSCLC cells via TRIM31-dependent MEF2C K63-linked polyubiquitination.BMC cancer · 2025Article
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- Reversible Acetylation of Non-histone Proteins in Human Cancers.Results and problems in cell differentiation · 2025Review
- Anticancer activity of RM-3-22: a TAZQ-based hydroxamic acid derivative targeting NSCLC in vitro and in vivo.Frontiers in pharmacology · 2025Article
- The role of complement in tumor immune tolerance and drug resistance: a double-edged sword.Frontiers in immunology · 2025Review
- GDF15 is associated with thyroid cancer progression and may modulate thyroid cancer cell senescence in a p53-dependent manner.Frontiers in endocrinology · 2025Article
- Preparation, characterization, and anticancer effects of an inclusion complex of coixol with β-cyclodextrin polymers.Pharmaceutical biology · 2024Article
- Multi-index comprehensive evaluation of the efficacy and response mechanism of immunotherapy in non-small cell lung cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- Macrophages as a Source and Target of GDF-15.International journal of molecular sciences · 2024Review
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- Transcriptomic and metabolomic analyses reveal the spatial role of carnitine metabolism in the progression of hepatitis B virus cirrhosis to hepatocellular carcinoma.Frontiers in microbiology · 2024Article
- Exploring acenocoumarol and silodosin in non-small cell lung cancer: Insights into EGFR-linked signaling mechanisms.F1000Research · 2024Article
- IL-17 induces NSCLC cell migration and invasion by elevating MMP19 gene transcription and expression through the interaction of p300-dependent STAT3-K631 acetylation and its Y705-phosphorylation.Oncology research · 2024Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and multiple evidence has confirmed that C5a production is elevated in NSCLC microenvironment. Although NSCLC cell proliferation induced by C5a has been reported, the involved mechanism has not been elucidated. In this study, we examined the proliferation-related genes (i.e., KLF5, GCN5, and GDF15) and C5a receptor (C5aR) expression in tumor tissues as well as C5a concentration in plasma of NSCLC patients, and then determined the roles of KLF5, GCN5, and GDF15 in C5a-triggered NSCLC cell proliferation and the related mechanism both in vitro and in vivo. Our results found that the expression of KLF5, GCN5, GDF15, C5aR, and C5a was significantly upregulated in NSCLC patients. Mechanistic exploration in vitro revealed that C5a could facilitate A549 cell proliferation through increasing KLF5, GCN5, and GDF15 expression. Besides, KLF5 and GCN5 could form a complex, binding to GDF15 promoter in a KLF5-dependent manner and leading to GDF15 gene transcription. More importantly, GCN5-mediated KLF5 acetylation contributing to GDF15 gene transcription and cell proliferation upon C5a stimulation, the region (-103 to +58 nt) of GDF15 promoter which KLF5 could bind to, and two new KLF5 lysine sites (K335 and K391) acetylated by GCN5 were identified for the first time. Furthermore, our experiment in vivo demonstrated that the growth of xenograft tumors in BALB/c nude mice was greatly suppressed by the silence of KLF5, GCN5, or GDF15. Collectively, these findings disclose that C5a-driven KLF5-GCN5-GDF15 axis had a critical role in NSCLC proliferation and might serve as targets for NSCLC therapy.
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