ArticleJournal of the Chinese Medical Association : JCMA2026
Single-cell omics in investigating the effect of CAFs with KRAS overexpression on the malignant progression of anaplastic thyroid cancer.
Article in Journal of the Chinese Medical Association : JCMA, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundAnaplastic thyroid cancer (ATC) is a highly aggressive malignancy with few effective treatments. Although the KRAS gene has been implicated in the progression of thyroid cancer, its specific mechanism in ATC remains unclear. This study aims to reveal the impact of cancer-associated fibroblasts (CAFs) with KRAS overexpression on the malignant biological behavior of ATC.
methodsThe single-cell RNA sequencing (scRNA-seq) was used to analyze the KRAS expression profile of fibroblasts (Fibs) in ATC progression, including cell subpopulation identification, KRAS distribution across different cell types, and functional pathway enrichment. Paracancerous tissue fibroblasts (PTFs) and CAFs were co-cultivated with ATC cells, respectively, and were treated with KRAS inhibitor BI-2865. Western blot, colony formation assay, 5-ethynyl-2'-deoxyuridine (EdU) staining, Transwell, and Annexin V-fluorescein isothiocyanate/propidium iodide (FITC/PI) staining were used to analyze the effects of KRAS on the proliferation, migration, and invasion abilities of ATC cells, as well as its influence on downstream signaling pathways.
resultsIn contrast to papillary thyroid cancer (PTC), the proportion of Fibs significantly increased in ATC, with KRAS observed to be highly expressed in Fibs. Further analysis revealed that Fib_KRAS+, which was highly expressed in ATC samples, did not show expression in PTC samples. In vitro cell experiments confirmed that CAFs with KRAS overexpression enhanced the proliferation, migration, and invasion of ATC cells and activated the downstream signaling pathway rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase (MAPK).
conclusionIn summary, CAFs with KRAS overexpression play a crucial role in the malignant biological characteristics of ATC. Targeting KRAS may be a potential strategy to effectively curb the malignant progression of ATC.
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