ArticleActa pharmacologica Sinica2024
Parkin deficiency promotes liver cancer metastasis by TMEFF1 transcription activation via TGF-β/Smad2/3 pathway.
Article in Acta pharmacologica Sinica, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 11 citations in OpenAlex.
- The parkin-γ-tubulin axis regulates epidermal homeostasis and is associated with the susceptibility to psoriasis.Cell death and differentiation · 2026Article
- Notch3 mediated TGF‑β1 activation enhances epithelial‑mesenchymal transition and cancer stemness in non‑small lung cancer.International journal of oncology · 2025Article
- Ginsenoside Rb1 attenuates erythropoietin-exacerbated vascular calcification in chronic kidney disease through BMP2-dependent Smad1/5/9 inhibition.CytoJournal · 2025Article
- Epithelial-mesenchymal plasticity in cancer: signaling pathways and therapeutic targets.MedComm · 2024Review
- Heparan sulfate 6-O-sulfotransferase 2 promotes gastric cancer progression by modulating the TGF-β/smad2/3 pathway.American journal of translational research · 2024Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
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Abstract
Parkin (PARK2) deficiency is frequently observed in various cancers and potentially promotes tumor progression. Here, we showed that Parkin expression is downregulated in liver cancer tissues, which correlates with poor patient survival. Parkin deficiency in liver cancer cells promotes migration and metastasis as well as changes in EMT and metastasis markers. A negative correlation exists between TMEFF1 and Parkin expression in liver cancer cells and tumor tissues. Parkin deficiency leads to upregulation of TMEFF1 which promotes migration and metastasis. TMEFF1 transcription is activated by Parkin-induced endogenous TGF-β production and subsequent phosphorylation of Smad2/3 and its binding to TMEFF1 promotor. TGF-β inhibitor and TMEFF1 knockdown can reverse shParkin-induced cell migration and changes of EMT markers. Parkin interacts with and promotes the ubiquitin-dependent degradation of HIF-1α/HIF-1β and p53, which accounts for the suppression of TGF-β production. Our data have revealed that Parkin deficiency in cancer leads to the activation of the TGF-β/Smad2/3 pathway, resulting in the expression of TMEFF1 which promotes cell migration, EMT, and metastasis in liver cancer cells.
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