ArticleBritish journal of cancer2021
Suppression of pancreatic cancer liver metastasis by secretion-deficient ITIH5.
Article in British journal of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- A Comprehensive Analysis of the ITIH Family Across Multiple Cancer Types and an Initial Investigation of ITIH1 in Gastric Cancer.Current medicinal chemistry · 2026Article
- ITIH5-mediated fibroblast/macrophage crosstalk exacerbates cardiac remodelling after myocardial infarction.Journal of translational medicine · 2025Article
- Strategies for Pancreatic Cancer-Responsive Nanodrug Platforms Targeting Tumor Hypoxic Environments.International journal of nanomedicine · 2025Review
- High Expression of the Tumor Suppressor Protein ITIH5 in Cholangiocarcinomas Correlates with a Favorable Prognosis.Cancers · 2024Article
- ITIH5 as a multifaceted player in pancreatic cancer suppression, impairing tyrosine kinase signaling, cell adhesion and migration.Molecular oncology · 2024Article
- An Overview on the Emerging Role of the Plasma Protease Inhibitor Protein ITIH5 as a Metastasis Suppressor.Cell biochemistry and biophysics · 2024Review
- Serum ITIH5 as a novel diagnostic biomarker in cholangiocarcinoma.Cancer science · 2024Article
- White Paper: Mimetics of Class 2 Tumor Suppressor Proteins as Novel Drug Candidates for Personalized Cancer Therapy.Cancers · 2022Article
- MUC16 Promotes Liver Metastasis of Pancreatic Ductal Adenocarcinoma by Upregulating NRP2-Associated Cell Adhesion.Molecular cancer research : MCR · 2022Article
- ITIH5-Derived Polypeptides Covering the VIT Domain Suppress the Growth of Human Cancer Cells In Vitro.Cancers · 2022Article
- Risk factors and predictive nomograms for early death of patients with pancreatic cancer liver metastasis: A large cohort study based on the SEER database and Chinese population.Frontiers in oncology · 2022Article
- ITIH5, a p53-responsive gene, inhibits the growth and metastasis of melanoma cells by downregulating the transcriptional activity of KLF4.Cell death & disease · 2021Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundPreviously, we identified ITIH5 as a suppressor of pancreatic ductal adenocarcinoma (PDAC) metastasis in experimental models. Expression of ITIH5 correlated with decreased cell motility, invasion and metastasis without significant inhibition of primary tumour growth. Here, we tested whether secretion of ITIH5 is required to suppress liver metastasis and sought to understand the role of ITIH5 in human PDAC.
methodsWe expressed mutant ITIH5 with deletion of the N-terminal secretion sequence (ITIH5Δs) in highly metastatic human PDAC cell lines. We used a human tissue microarray (TMA) to compare ITIH5 levels in uninvolved pancreas, primary and metastatic PDAC.
resultsSecretion-deficient ITIH5Δs was sufficient to suppress liver metastasis. Similar to secreted ITIH5, expression of ITIH5Δs was associated with rounded cell morphology, reduced cell motility and reduction of liver metastasis. Expression of ITIH5 is low in both human primary PDAC and matched metastases.
conclusionsMetastasis suppression by ITIH5 may be mediated by an intracellular mechanism. In human PDAC, loss of ITIH5 may be an early event and ITIH5-low PDAC cells in primary tumours may be selected for liver metastasis. Further defining the ITIH5-mediated pathway in PDAC could establish future therapeutic exploitation of this biology and reduce morbidity and mortality associated with PDAC metastasis.
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