ArticleProceedings of the National Academy of Sciences of the United States of America2018
Cancer-associated fibroblasts suppress SOX2-induced dysplasia in a lung squamous cancer coculture.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Advancing lung organoids toward clinical applications: a global perspective on research focus and future directions.Frontiers in medicine · 2025Pooled it
- Matrix Stiffness Modulates 3D Spheroid-Derived Extracellular Vesicle Profiles and Discovery of Piezo1 Cargo.Cellular and molecular bioengineering · 2026Article
- The role of the tumor microenvironment in drug resistance acquisition in lung squamous cell carcinoma.Journal of experimental & clinical cancer research : CR · 2026Review
- Dual Graphene Oxide-Based Multigene Delivery for Cancer Elimination via Stromal and Immune Reprogramming.International journal of biomaterials · 2026Article
- Unveiling the roles of SPP1Genes & diseases · 2026Article
- A single-cell and tissue-scale analysis suite resolves Mixl1's role in heart development.iScience · 2025Article
- Lung cancer organoids: a new strategy for precision medicine research.Translational lung cancer research · 2025Review
- MACC1 ablation suppresses the dedifferentiation process of non-CSCs in lung cancer through stabilizing KLF4.Cell death discovery · 2024Article
- The importance of 3D fibre architecture in cancer and implications for biomaterial model design.Nature reviews. Cancer · 2024Review
- Patient-derived tumor organoids: a new avenue for preclinical research and precision medicine in oncology.Experimental & molecular medicine · 2024Review
- Promising preclinical models for lung cancer research-lung cancer organoids: a narrative review.Translational lung cancer research · 2024Review
- Article
- Population-based high-dimensional analyses identify multiple intrinsic characters for cancer vaccines against lung squamous cell carcinoma.Medical oncology (Northwood, London, England) · 2024Article
- Patient-derived organoid culture in epithelial ovarian cancers-Techniques, applications, and future perspectives.Cancer medicine · 2023Review
- Review
- A 3D culture system for evaluating the combined effects of cisplatin and anti-fibrotic drugs on the growth and invasion of lung cancer cells co-cultured with fibroblasts.APL bioengineering · 2023Article
- Key aspects for conception and construction of co-culture models of tumor-stroma interactions.Frontiers in bioengineering and biotechnology · 2023Review
- Lung cancer organoids: models for preclinical research and precision medicine.Frontiers in oncology · 2023Review
- Application status and future prospects of the PDX model in lung cancer.Frontiers in oncology · 2023Review
- Dual Role of Fibroblasts Educated by Tumour in Cancer Behavior and Therapeutic Perspectives.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumorigenesis depends on intricate interactions between genetically altered tumor cells and their surrounding microenvironment. While oncogenic drivers in lung squamous carcinoma (LUSC) have been described, the role of stroma in modulating tissue architecture, particularly cell polarity, remains unclear. Here, we report the establishment of a 3D coculture system of LUSC epithelial cells with cancer-associated fibroblasts (CAFs) and extracellular matrix that together capture key components of the tumor microenvironment (TME). Single LUSC epithelial cells develop into acinar-like structures with 0.02% efficiency, and addition of CAFs provides proper tumor-stromal interactions within an appropriate 3D architectural context. Using this model, we recapitulate key pathological changes during tumorigenesis, from hyperplasia to dysplasia and eventually invasion, in malignant LUSC spheroids that undergo phenotypic switching in response to cell intrinsic and extrinsic changes. Overexpression of SOX2 is sufficient to mediate the transition from hyperplasia to dysplasia in LUSC spheroids, while the presence of CAFs makes them invasive. Unexpectedly, CAFs suppress the activity of high SOX2 levels, restore hyperplasia, and enhance the formation of acinar-like structures. Taken together, these observations suggest that stromal factors can override cell intrinsic oncogenic changes in determining the disease phenotype, thus providing fundamental evidence for the existence of dynamic reciprocity between the nucleus and the TME of LUSC.
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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.