ArticleMolecular oncology2019
Klotho-mediated targeting of CCL2 suppresses the induction of colorectal cancer progression by stromal cell senescent microenvironments.
Article in Molecular oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 46 citations in OpenAlex.
- Characterizing the SASP-Dependent Paracrine Spreading of Senescence Between Human Brain Cell Types.Aging cell · 2026Article
- Cancer-associated fibroblasts are associated with CD8+ T cell depletion and poor prognosis in colorectal adenocarcinoma: a multi-omics and machine learning analysis.The journal of pathology. Clinical research · 2026Article
- Network modeling of sporadic colorectal cancer reveals the importance of off-target effects of Cyclooxygenase inhibitors.NPJ systems biology and applications · 2026Article
- Characterizing the SASP-Dependent Paracrine Spreading of Senescence Between Human Brain Cell Types.bioRxiv : the preprint server for biology · 2026Article
- Article
- Review
- Differential expression of ferroptosis markers, circadian regulators, KLOTHO, and classical tumor suppressors in colorectal cancer according to tumor stage: Influence of age, anatomical location, and correlation patterns.Histology and histopathology · 2025Article
- Diabetes reshapes pancreatic cancer-associated endothelial niche by accelerating senescence.Nature communications · 2025Article
- Immunosenescence and cancer: molecular hallmarks, tumor microenvironment remodeling, and age-specific immunotherapy challenges.Journal of hematology & oncology · 2025Review
- Comparative analysis of gene regulation in single cells using Compass.Cell reports methods · 2025Article
- The Impact of Klotho in Cancer: From Development and Progression to Therapeutic Potential.Genes · 2025Review
- Role of Senescence-Associated Biomarkers and Immune Dynamics in Predicting Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer.International journal of general medicine · 2025Article
- Cellular senescence in colorectal cancer: its occurrence, effect and therapy.Frontiers in oncology · 2025Review
- Cellular senescence and SASP in tumor progression and therapeutic opportunities.Molecular cancer · 2024Review
- Deciphering Glioblastoma: Fundamental and Novel Insights into the Biology and Therapeutic Strategies of Gliomas.Current issues in molecular biology · 2024Review
- SKN-1/NRF2 upregulation by vitamin A is conserved from nematodes to mammals and is critical for lifespan extension in Caenorhabditis elegans.Aging cell · 2024Article
- Biomarkers of lymph node metastasis in colorectal cancer: update.Frontiers in oncology · 2024Review
- Klotho in Cancer: Potential Diagnostic and Prognostic Applications.Diagnostics (Basel, Switzerland) · 2023Review
- Hypothesis: functional age and onset of autosomal dominant genetic prion disease.Theory in biosciences = Theorie in den Biowissenschaften · 2023Article
- Effects of regorafenib on the mononuclear/phagocyte system and how these contribute to the inhibition of colorectal tumors in mice.European journal of medical research · 2023Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Senescent microenvironments play an important role in tumor progression. Here, we report that doxorubicin (DOX)-pretreated or replicative senescent stromal cells (WI-38 and HUVEC) promote colorectal cancer (CRC) cell growth and invasion in vitro and in vivo. These pro-tumorigenic effects were attenuated by exogenous administration of Klotho, an anti-aging factor. We subsequently identified several senescence-associated secretory phenotype (SASP)-associated genes, including CCL2, which were significantly upregulated in both types of senescent stromal cells during replication and DNA damage-induced senescence. Importantly, we found that the secretion of CCL2 by senescent stromal cells was significantly higher than that seen in nonsenescent cells or in senescent cells pretreated with Klotho. Notably, CCL2 was found to accelerate CRC cell proliferation and invasion, while this effect could be blocked by administration of a specific CCR2 antagonist. We further show that Klotho can suppress NF-κB activation during DOX-induced senescence and thus block CCL2 transcription. Low expression of Klotho, or high expression of CCL2 in patient tumor tissues, correlated with poor overall survival of CRC patients. Collectively, our findings suggest that senescent stromal cells are linked to progression of CRC. Klotho can suppress the senescent stromal cell-associated triggering of CRC progression by inhibiting the expression of SASP factors including CCL2. The identification of key SASP factors such as CCL2 may provide potential therapeutic targets for improving CRC therapy.
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