ArticleThe Journal of clinical investigation2023
The UBE2C/CDH1/DEPTOR axis is an oncogene and tumor suppressor cascade in lung cancer cells.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 64 citations in OpenAlex.
- UBE2C promotes pancreatic cancer progression through PI3K/Akt/mTOR signaling pathway.Cell cycle (Georgetown, Tex.) · 2026Article
- UBE2C-TRIM21-driven NOS2 degradation stabilizes Tregs and suppresses pyroptotic signaling in thyrocytes in Hashimoto's thyroiditis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- MECP2Science China. Life sciences · 2026Article
- Deciphering lung cancer at high resolution: a narrative review of applications of single-cell and spatial transcriptomics sequencing.Translational lung cancer research · 2026Review
- UBE2C at the crossroads of cell cycle regulation and DNA damage response in cancer.Cell biology and toxicology · 2026Review
- TPX2 as a prognostic biomarker and potential therapeutic target for malignant melanoma proliferation and metastasis.Experimental and therapeutic medicine · 2026Article
- Pancancer Fine-Mapping of Mutational Intolerance Identifies CHEK1 as an Immunosuppressive Driver in Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Identification of key genes as diagnostic biomarkers for lung adenocarcinoma using bioinformatics and machine learning.Discover oncology · 2026Article
- [Glutamine-induced autophagy exacerbates muscle atrophy in cachectic nude mice: a multi-omics analysis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- MAZ-Mediated ubiquitin-conjugating enzyme E2C upregulation promotes breast cancer progression via the MAPK signaling pathway.Translational oncology · 2026Article
- SUMOylation of UBE2C facilitates hepatocellular carcinoma proliferation and invasion via the MAPK pathway.Translational cancer research · 2026Article
- Advances in protein ubiquitination modification and immune evasion of breast cancer.Frontiers in cell and developmental biology · 2026Review
- MiRNA-140-3p affects the proliferation and metastasis of osteosarcoma via the UBE2C/PI3K-Akt axis.Frontiers in oncology · 2026Article
- Ubiquitin-conjugating Enzymes in Cancer.International journal of biological sciences · 2026Review
- KDM5C-regulated SIX5 promotes glioblastoma progression through transcriptional activation of UBE2C and enhancement of the Warburg effect.Frontiers in immunology · 2026Article
- Article
- A Mendelian randomization-based risk model using aging-related genes for prognosis in lung adenocarcinoma.Discover oncology · 2025Article
- Investigating Germ Cell Transition Genes in Breast Cancer: Exploring the Genesis of Cancer Testis-Associated Markers.International journal of molecular sciences · 2025Article
- UBE2C-mediated ubiquitination of ACSL4 inhibits ferroptosis and promotes gastric cancer progression.Discover oncology · 2025Article
- Inhibition of UBE2C Promotes Parkin-Mediated K63-Linked Ubiquitination of TOP2A to Induce Senescence and Increase Sensitivity of Doxorubicin in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
6 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ubiquitin-conjugating enzyme E2C (UBE2C) mediates ubiquitylation chain formation via the K11 linkage. While previous in vitro studies showed that UBE2C plays a growth-promoting role in cancer cell lines, the underlying mechanism remains elusive. Still unknown is whether and how UBE2C plays a promoting role in vivo. Here we report that UBE2C was indeed essential for growth and survival of lung cancer cells harboring Kras mutations, and UBE2C was required for KrasG12D-induced lung tumorigenesis, since Ube2c deletion significantly inhibited tumor formation and extended the lifespan of mice. Mechanistically, KrasG12D induced expression of UBE2C, which coupled with APC/CCDH1 E3 ligase to promote ubiquitylation and degradation of DEPTOR, leading to activation of mTORC signaling. Importantly, DEPTOR levels fluctuated during cell cycle progression in a manner dependent on UBE2C and CDH1, indicating their physiological connection. Finally, Deptor deletion fully rescued the tumor inhibitory effect of Ube2c deletion in the KrasG12D lung tumor model, indicating a causal role of Deptor. Taken together, our study shows that the UBE2C/CDH1/DEPTOR axis forms an oncogene and tumor suppressor cascade that regulates cell cycle progression and autophagy and validates UBE2C an attractive target for lung cancer associated with Kras mutations.
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