ArticleCell death & disease2022
RNF12 is regulated by AKT phosphorylation and promotes TGF-β driven breast cancer metastasis.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- UBE2S promotes gastric cancer progression through RACGAP1 stabilization associated with K292-dependent K63-linked ubiquitination.Cancer biology & therapy · 2026Article
- Preclinical models of breast cancer metastasis: strengths, limitations, and clinical relevance.NPJ breast cancer · 2026Review
- A novel kinase inhibitor, Regorafenib, blocks EGFR-dependent signaling to repress tumour metastasis in human triple-negative breast cancers.Frontiers in cell and developmental biology · 2026Article
- Ubiquitination in cancer: mechanisms and therapeutic opportunities.Cancer communications (London, England) · 2025Review
- Fibronectin 1 Aggravates Colon Cancer Metastasis by Regulating RAP1B Protein Stability Through Akt/CREB Signalling Pathway.Journal of cellular and molecular medicine · 2025Article
- Tumor microenvironment modulation by SERPINE1 increases radioimmunotherapy in murine model of gastric cancer.Scientific reports · 2025Article
- Dual signaling pathways of TGF-β superfamily cytokines in hepatocytes: balancing liver homeostasis and disease progression.Frontiers in pharmacology · 2025Review
- Ubiquitination in osteosarcoma: unveiling the impact on cell biology and therapeutic strategies.Cancer biology & medicine · 2024Review
- Ononin inhibits triple-negative breast cancer lung metastasis by targeting the EGFR-mediated PI3K/Akt/mTOR pathway.Science China. Life sciences · 2024Article
- (E)-2-Methoxy-4-(3-(4-Methoxyphenyl) Prop-1-en-1-yl) Phenol Suppresses Breast Cancer Progression by Dual-Regulating VEGFR2 and PPARγ.Journal of microbiology and biotechnology · 2024Article
- Cholesterol modulates type I/II TGF-β receptor complexes and alters the balance between Smad and Akt signaling in hepatocytes.Communications biology · 2024Article
- The effects of the tumor suppressor geneTranslational cancer research · 2023Article
- MicroRNA PC-3p-2869 Regulates Antler Growth and Inhibits Proliferation and Migration of Human Osteosarcoma and Chondrosarcoma Cells by Targeting CDK8, EEF1A1, and NTN1.International journal of molecular sciences · 2023Article
- Review
- Ring finger protein 12 activates AKT signalling to promote the progression of liver cancer by interacting with EGFR.Journal of cellular and molecular medicine · 2023Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor-β (TGF-β) acts as a pro-metastatic factor in advanced breast cancer. RNF12, an E3 ubiquitin ligase, stimulates TGF-β signaling by binding to the inhibitory SMAD7 and inducing its proteasomal degradation. How RNF12 activity is regulated and its exact role in cancer is incompletely understood. Here we report that RNF12 was overexpressed in invasive breast cancers and its high expression correlated with poor prognosis. RNF12 promoted breast cancer cell migration, invasion, and experimental metastasis in zebrafish and murine xenograft models. RNF12 levels were positively associated with the phosphorylated AKT/protein kinase B (PKB) levels, and both displayed significant higher levels in the basal-like subtype compared with the levels in luminal-like subtype of breast cancer cells. Mechanistically, AKT-mediated phosphorylation induced the nuclear localization of RNF12, maintained its stability, and accelerated the degradation of SMAD7 mediated by RNF12. Furthermore, we demonstrated that RNF12 and AKT cooperated functionally in breast cancer cell migration. Notably, RNF12 expression strongly correlated with both phosphorylated AKT and phosphorylated SMAD2 levels in breast cancer tissues. Thus, our results uncovered RNF12 as an important determinant in the crosstalk between the TGF-β and AKT signaling pathways during breast cancer progression.
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