ArticleMolecular oncology2021
Tspan5 promotes epithelial-mesenchymal transition and tumour metastasis of hepatocellular carcinoma by activating Notch signalling.
Article in Molecular oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- Targeting ferroptosis induction via nanomaterials in hepatocellular carcinoma: an insight into mechanism and therapeutic potential.Journal of nanobiotechnology · 2026Review
- Multi-omics analysis and experimental validation uncovers prognosis significance of IKBIP in patients with hepatocellular carcinoma: a multicenter cohort study.BMC gastroenterology · 2026Article
- Cldn11 deficiency aggravates osteoarthritis by inhibiting Notch signalling in a Tspan5-dependent manner.Journal of orthopaedic surgery and research · 2026Article
- Current research of the Notch pathway in hepatocellular carcinoma.European journal of medical research · 2025Review
- Hepatocellular carcinoma: signaling pathways and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Antiviral therapy for hepatitis B virus infection is beneficial for the prognosis hepatocellular carcinoma.World journal of gastrointestinal oncology · 2025Article
- Migrasome-Related Prognostic Genes in Gastric Cancer: A Transcriptomic and Immunotherapeutic Analysis.OncoTargets and therapy · 2025Article
- Article
- Notch signaling in cancers: mechanism and potential therapy.Frontiers in cell and developmental biology · 2025Review
- Study on the mechanism by which Xuanfu Hua Tang increases sensitivity of hepatocellular carcinoma cells to sorafenib by antagonizing the Notch1 pathway through HIF-2α.Frontiers in oncology · 2025Article
- NOTCH3 promotes malignant progression of bladder cancer by directly regulating SPP1 and activating PI3K/AKT pathway.Cell death & disease · 2024Article
- Tetraspanins in digestive‑system cancers: Expression, function and therapeutic potential (Review).Molecular medicine reports · 2024Review
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- The role of Tetraspanins in digestive system tumor development: update and emerging evidence.Frontiers in cell and developmental biology · 2024Review
- Cross talk between tumor stemness and microenvironment for prognosis and immunotherapy of uveal melanoma.Journal of cancer research and clinical oncology · 2023Article
- Modulation of Notch Signaling by Small-Molecular Compounds and Its Potential in Anticancer Studies.Cancers · 2023Review
- Integrated single-cell and bulk RNA sequencing analysis identifies a prognostic signature related to ferroptosis dependence in colorectal cancer.Scientific reports · 2023Article
- High Expression of Tetraspanin 5 as a Prognostic Marker of Colorectal Cancer.International journal of molecular sciences · 2023Article
- The role of Hedgehog and Notch signaling pathway in cancer.Molecular biomedicine · 2022Review
- Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide due to a high rate of tumour metastasis and disease recurrence. In physiological conditions, tetraspanins interact with specific partner proteins in tetraspanin-enriched microdomains and regulate their subcellular localization and function. However, the function of Tspan5 in pathological processes, particularly in cancer biology and its clinical significance, are still unclear. Here, we describe that a high expression of Tspan5 is significantly associated with some clinicopathological features including invasive length, vascular invasion, clinical stage and poor overall survival of HCC patients. Alterations of Tspan5 expression by lentivirus transductions in HCC cells demonstrated that Tspan5 promotes wound healing and cell migration in vitro and tumour metastasis of HCC cells in vivo. Mechanistic studies revealed that Tspan5 promoted cell migration and tumour metastasis by increasing the enzymatic maturation of ADAM10 and activating Notch signalling via the increase of the cleavage of the Notch1 receptor catalysed by the γ-secretase complex. Activation of Notch signalling by Tspan5 was shown further to enhance the epithelial-mesenchymal transition (EMT) and actin skeleton rearrangement of tumour cells. In clinical HCC samples, Tspan5 expression is strongly correlated with many key molecules acting in Notch signalling and EMT, highlighting the role of Tspan5 in the regulation of Notch signalling, EMT and tumour metastasis of HCC. Our findings provide new insights into the mechanism of tumour metastasis and disease progression of HCC and may facilitate the development of novel clinical intervention strategies against HCC.
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Registered trials
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