ArticleThe Journal of experimental medicine2013
Chemotherapy activates cancer-associated fibroblasts to maintain colorectal cancer-initiating cells by IL-17A.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 225 papers, 1 of them a synthesis that pooled it.
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Who cites it
225 citing papers in PubMed, 1 synthesis or guideline pooled it, 352 citations in OpenAlex.
- Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review.Molecular cancer · 2019Pooled it
- Multi-Omics Integration Identifies Epithelial-Stromal-Immune Co-Regulators Bridging Ulcerative Colitis and Colorectal Cancer.Biomedicines · 2026Article
- Fibroblasts: a diverse population of cells balancing homeostasis, wound healing, regeneration, inflammation, fibrosis, and cancer across organs.JCI insight · 2026Review
- Gold- and Platinum-Peptide Bioconjugates in Cancer Therapy: Recent Advances and Future Directions.Pharmaceutics · 2026Review
- Cytokines and cancer-associated fibroblasts.Journal of hematology & oncology · 2026Review
- Defining the tumor microenvironment of non-small cell lung cancer.Immunology and cell biology · 2026Review
- Validation of chemoresistance phenotypes in pleural mesothelioma across 2D, 3D, and in vivo models.Scientific reports · 2026Article
- Cancer-associated fibroblast-derived GAS6 increases resistance to chemotherapy through AXL/STAT3/ABCG1 in gastric cancer.British journal of cancer · 2026Article
- Targeting cytokine and chemokine signaling pathways for enhancing chemo-sensitivity in colorectal cancer.Cell communication and signaling : CCS · 2025Review
- Comparative analysis of 3D-culture techniques for multicellular colorectal tumour spheroids and development of a novel SW48 3D-model.Scientific reports · 2025Article
- Reporter-based screening identifies RAS-RAF mutations as drivers of resistance to active-state RAS inhibitors in colorectal cancer.Science signaling · 2025Article
- Comprehensive genomic and transcriptomic analyses reveal prognostic stratification for esophageal squamous cell carcinoma.Signal transduction and targeted therapy · 2025Article
- KRAS regulates IL-17 signal activity by affect the metastasis of osteosarcoma via an IL-17A-dependent manner.JBMR plus · 2025Article
- Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.Journal of hematology & oncology · 2025Review
- Desmoplastic reaction in the microenvironment of head and neck and other solid tumors: the therapeutic barrier.Therapeutic advances in medical oncology · 2025Review
- Current perspectives and trends in colorectal cancer and cancer-associated fibroblasts: a review and bibliometric analysis.Frontiers in immunology · 2025Review
- Unraveling the role of cancer-associated fibroblasts in colorectal cancer.World journal of gastrointestinal oncology · 2024Review
- Fibrosis-Encapsulated Tumoroid, A Solid Cancer Assembloid Model for Cancer Research and Drug Screening.Advanced healthcare materials · 2024Article
- Article
- Intestinal stem cells in intestinal homeostasis and colorectal tumorigenesis.Life medicine · 2024Review
165 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Many solid cancers display cellular hierarchies with self-renewing, tumorigenic stemlike cells, or cancer-initiating cells (CICs) at the apex. Whereas CICs often exhibit relative resistance to conventional cancer therapies, they also receive critical maintenance cues from supportive stromal elements that also respond to cytotoxic therapies. To interrogate the interplay between chemotherapy and CICs, we investigated cellular heterogeneity in human colorectal cancers. Colorectal CICs were resistant to conventional chemotherapy in cell-autonomous assays, but CIC chemoresistance was also increased by cancer-associated fibroblasts (CAFs). Comparative analysis of matched colorectal cancer specimens from patients before and after cytotoxic treatment revealed a significant increase in CAFs. Chemotherapy-treated human CAFs promoted CIC self-renewal and in vivo tumor growth associated with increased secretion of specific cytokines and chemokines, including interleukin-17A (IL-17A). Exogenous IL-17A increased CIC self-renewal and invasion, and targeting IL-17A signaling impaired CIC growth. Notably, IL-17A was overexpressed by colorectal CAFs in response to chemotherapy with expression validated directly in patient-derived specimens without culture. These data suggest that chemotherapy induces remodeling of the tumor microenvironment to support the tumor cellular hierarchy through secreted factors. Incorporating simultaneous disruption of CIC mechanisms and interplay with the tumor microenvironment could optimize therapeutic targeting of cancer.
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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.