ArticleOncogene2014
ISGylation governs the oncogenic function of Ki-Ras in breast cancer.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
55 citing papers in PubMed, 89 citations in OpenAlex.
- Understanding protein ISGylation, a multifaceted posttranslational modification.Cell chemical biology · 2026Review
- TRIM Protein Superfamily in Breast Cancer: Yin and Yang.Biochemical genetics · 2026Review
- Inflammatory monocytes constrain YAP-induced cell proliferation.Science advances · 2026Article
- SEMA6A inhibits tumor progression and boosts anti-tumor immunity via blocking the ISG15/TGFβ axis in colorectal cancer.Molecular biomedicine · 2026Article
- JAK/STAT1-interferon-ISGylation networks in breast cancer resistance to inhibitors of FOXM1 and CDK4/6.NPJ breast cancer · 2026Article
- Unraveling the Biology of Interferon-Stimulated Genes: Mechanisms, Functions, and Clinical Implications.Infection and drug resistance · 2026Review
- The ISGylation tapestry in cancer: weaving phenotypic plasticity through multidimensional regulatory looms.Cellular & molecular biology letters · 2025Review
- Review
- Article
- ISGylation: is our genome yearning for such a modification?Acta biochimica et biophysica Sinica · 2025Review
- HERC5/ISG15 Enhances Glioblastoma Stemness and Tumor Progression by mediating SERBP1protein stability.Neuromolecular medicine · 2025Article
- Resolving tumor microenvironment heterogeneity to forecast immunotherapy response in triple-negative breast cancer through multi-scale analysis.Frontiers in oncology · 2025Article
- Molecular Interplay of ISG15/ISGylation in Neuropathologies.CNS & neurological disorders drug targets · 2025Review
- SIRT1 ISGylation accelerates tumor progression by unleashing SIRT1 from the inactive state to promote its deacetylase activity.Experimental & molecular medicine · 2024Article
- Inhibition of ADAM9 promotes the selective degradation of KRAS and sensitizes pancreatic cancers to chemotherapy.Nature cancer · 2024Article
- ISG15 mediates the function of extracellular vesicles in promoting ovarian cancer progression and metastasis.Journal of extracellular biology · 2024Article
- Unveiling the Multifaceted Roles of ISG15: From Immunomodulation to Therapeutic Frontiers.Vaccines · 2024Review
- ISG15: A link between innate immune signaling, DNA replication, and genome stability.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Review
- The Functional Roles of ISG15/ISGylation in Cancer.Molecules (Basel, Switzerland) · 2023Review
- Protein ISGylation: a posttranslational modification with implications for malignant neoplasms.Exploration of targeted anti-tumor therapy · 2023Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant expression of the oncogenic Kirsten-Ras (Ki-Ras) and interferon-stimulated gene 15 (ISG15) pathways is common in breast and other cancers. However, whether these dysregulated pathways cooperate to promote malignancy is not known. This study links Ki-Ras and ISG15 in a previously unidentified regulatory loop that may underlie malignant transformation of mammary cells. We show that oncogenic Ki-Ras regulates the expression of the ISG15 pathway (free ISG15 and ISG15 conjugates), and ISG15, in turn, stabilizes Ki-Ras protein by inhibiting its targeted degradation via lysosomes in breast cancer cells. Disruption of this loop by silencing either Ki-Ras or the ISG15 pathway restored the disrupted cellular architecture, a hallmark feature of most cancer cells. We also demonstrate that ISG15 and UbcH8 (ISG15-specific conjugating enzyme) shRNAs reversed Ki-Ras mutation-associated phenotypes of cancer cells, such as increased cell proliferation, colony formation, anchorage-independent growth in soft agar, cell migration, and epithelial-mesenchymal transition. As UbcH8-silenced breast cancer cells are devoid of ISG15 conjugates but have free ISG15, our results using UbcH8-silenced cells suggest that ISG15 conjugates, and not free ISG15, contributes to oncogenic Ki-Ras transformation. We have thus identified the conjugated form of ISG15 as a critical downstream mediator of oncogenic Ki-Ras, providing a potential mechanistic link between ISG15 and Ki-Ras-mediated breast tumorigenesis. Our findings, which show that inhibition of the ISGylation reverses the malignant phenotypes of breast cancer cells expressing oncogenic Ki-Ras, support the development of ISG15 conjugation inhibitors for treating breast and also other cancers expressing oncogenic Ki-Ras.
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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.