ArticleJournal of experimental & clinical cancer research : CR2023
ISG15 and ISGylation modulates cancer stem cell-like characteristics in promoting tumor growth of anaplastic thyroid carcinoma.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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22 citing papers in PubMed, 25 citations in OpenAlex.
- ISGylation-mediated stabilization of CYP4Z1 fuels breast cancer initiation and progression.Experimental & molecular medicine · 2026Article
- [Preparation of retinoic acid and irinotecan co-loaded lipo-somes and theirZhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Article
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- YKL-40 alleviates the TNF-α-Induced chondrocyte injury in osteoarthritis in vitro.Scientific reports · 2026Article
- Identification and molecular typing of disulfidptosis-related biomarkers in anaplastic thyroid carcinoma.Cell death discovery · 2026Article
- ISG15-driven immune modulation and tumor progression in breast cancer metastasis: insights from single-cell and spatial transcriptomics.BMC medicine · 2026Article
- Single-cell omics in investigating the effect of CAFs with KRAS overexpression on the malignant progression of anaplastic thyroid cancer.Journal of the Chinese Medical Association : JCMA · 2026Article
- Tumor microenvironment-guided targeted and immunotherapy in anaplastic thyroid cancer: a literature review from preclinical models to clinical translation.Translational cancer research · 2026Review
- Study on the mechanism of TP53 degradation by SFN ubiquitination affecting locally advanced TC progression.Frontiers in chemistry · 2026Article
- A novel zinc finger protein gene signature for prognostic prediction, tumor microenvironment characterization, and therapeutic response in uterine corpus endometrial carcinoma.Scientific reports · 2025Article
- The ISGylation tapestry in cancer: weaving phenotypic plasticity through multidimensional regulatory looms.Cellular & molecular biology letters · 2025Review
- Bioinformatics analysis of IFI6 as a novel prognostic biomarker and its correlation with immune infiltration in breast cancer.Scientific reports · 2025Article
- Post-translational modifications in anaplastic thyroid carcinoma: biological mechanisms and therapeutic potential.Cancer cell international · 2025Review
- Anaplastic thyroid cancer: Genetic roles, targeted therapy, and immunotherapy.Genes & diseases · 2025Review
- Identification of stemness subtypes and prognostic modeling in thyroid cancer: the critical role of DPYSL3 in tumor progression and immune microenvironment.Discover oncology · 2025Article
- Elevation of ISG15 promotes diabetic kidney disease by modulating renal tubular epithelial cell pyroptosis.Clinical and translational medicine · 2025Article
- ISGylation: is our genome yearning for such a modification?Acta biochimica et biophysica Sinica · 2025Review
- Essential Regulation of Spermatogonial Stem Cell Fate Decisions and Male Fertility by APBB1 via Interaction with KAT5 and GDF15 in Humans and Mice.Research (Washington, D.C.) · 2025Article
- Correction: ISG15 and ISGylation modulates cancer stem cell-like characteristics in promoting tumor growth of anaplastic thyroid carcinoma.Journal of experimental & clinical cancer research : CR · 2024Article
- Review
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAnaplastic thyroid carcinoma (ATC) was a rare and extremely malignant endocrine cancer with the distinct hallmark of high proportion of cancer stem cell-like characteristics. Therapies aiming to cancer stem-like cells (CSCs) were emerging as a new direction in cancer treatment, but targeting ATC CSCs remained challenging, mainly due to incomplete insights of the regulatory mechanism of CSCs. Here, we unveiled a novel role of ISG15 in the modulation of ATC CSCs.
methodsThe expression of ubiquitin-like proteins were detected by bioinformatics and immunohistochemistry. The correlation between ISG15 expression and tumor stem cells and malignant progression of ATC was analyzed by single-cell RNA sequence from the Gene Expression Omnibus. Flow cytometry combined with immunofluorescence were used to verify the enrichment of ISG15 and ISGyaltion in cancer stem cells. The effect and mechanism of ISG15 and KPNA2 on cancer stem cell-like characteristics of ATC cells were determined by molecular biology experiments. Mass spectrometry combined with immunoprecipitation to screen the substrates of ISG15 and validate its ISGylation modification. Nude mice and zebrafish xenograft models were utilized to demonstrate that ISG15 regulates stem cell characteristics and promotes malignant progression of ATC.
resultsWe found that among several ubiquitin proteins, only ISG15 was aberrantly expressed in ATC and enriched in CSCs. Single-cell sequencing analysis revealed that abnormal expression of ISG15 were intensely associated with stemness and malignant cells in ATC. Inhibition of ISG15 expression dramatically attenuated clone and sphere formation of ATC cells, and facilitated its sensitivity to doxorubicin. Notably, overexpression of ISGylation, but not the non-ISGylation mutant, effectively reinforced cancer stem cell-like characteristics. Mechanistically, ISG15 mediated the ISGylation of KPNA2 and impeded its ubiquitination to promote stability, further maintaining cancer stem cell-like characteristics. Finally, depletion of ISG15 inhibited ATC growth and metastasis in xenografted mouse and zebrafish models.
conclusionOur studies not only provided new insights into potential intervention strategies targeting ATC CSCs, but also uncovered the novel biological functions and mechanisms of ISG15 and ISGylation for maintaining ATC cancer stem cell-like characteristics.
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