ArticleClinical & experimental metastasis2017
Genome-wide in vivo RNAi screen identifies ITIH5 as a metastasis suppressor in pancreatic cancer.
Article in Clinical & experimental metastasis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Targeting FGFR4 abrogates HNF1A-driven metastasis in pancreatic ductal adenocarcinoma.Molecular cancer · 2025Article
- High Expression of the Tumor Suppressor Protein ITIH5 in Cholangiocarcinomas Correlates with a Favorable Prognosis.Cancers · 2024Article
- An Overview on the Emerging Role of the Plasma Protease Inhibitor Protein ITIH5 as a Metastasis Suppressor.Cell biochemistry and biophysics · 2024Review
- ITIH5 as a multifaceted player in pancreatic cancer suppression, impairing tyrosine kinase signaling, cell adhesion and migration.Molecular oncology · 2024Article
- The function of the inter-alpha-trypsin inhibitors in the development of disease.Frontiers in medicine · 2024Review
- Metastasis suppressor genes in clinical practice: are they druggable?Cancer metastasis reviews · 2023Review
- Molecular differences of angiogenic versus vessel co-opting colorectal cancer liver metastases at single-cell resolution.Molecular cancer · 2023Article
- Urine inter-alpha-trypsin inhibitor family-related proteins may serve as biomarkers for disease activity of lupus.Journal of clinical laboratory analysis · 2022Article
- ITIH5-Derived Polypeptides Covering the VIT Domain Suppress the Growth of Human Cancer Cells In Vitro.Cancers · 2022Article
- Long noncoding RNA LINC00261 upregulates ITIH5 to impair tumorigenic ability of pancreatic cancer stem cells.Cell death discovery · 2021Article
- Article
- ITIH5, a p53-responsive gene, inhibits the growth and metastasis of melanoma cells by downregulating the transcriptional activity of KLF4.Cell death & disease · 2021Article
- Article
- Optimal therapeutic targeting by HDAC inhibition in biopsy-derived treatment-naïve diffuse midline glioma models.Neuro-oncology · 2021Article
- In Vivo Genome-Wide Pooled RNAi Screens in Cancer Cells to Identify Determinants of Chemotherapy/Drug Response.Methods in molecular biology (Clifton, N.J.) · 2021Article
- ITIH5 shows tumor suppressive properties in cervical cancer cells grown as multicellular tumor spheroids.American journal of translational research · 2021Article
- The Inter-α-Trypsin Inhibitor Family: Versatile Molecules in Biology and Pathology.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020Review
- Article
- The Impact of TCR Signal Strength on Resident Memory T Cell Formation during Influenza Virus Infection.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Using a Systems Biology Approach To Study Host-Pathogen Interactions.Microbiology spectrum · 2019Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
The overwhelming majority of pancreatic ductal adenocarcinoma (PDAC) is not diagnosed until the cancer has metastasized, leading to an abysmal average life expectancy (3-6 months post-diagnosis). Earlier detection and more effective treatments have been hampered by inadequate understanding of the underlying molecular mechanisms controlling metastasis. We hypothesized that metastasis suppressors are involved in controlling metastasis in pancreatic cancer. Using an unbiased genome-wide shRNA screen, an shRNA library was transduced into the non-metastatic PDAC line S2-028 followed by intrasplenic injection. Resulting liver metastases were individually isolated from these mice. One liver metastatic nodule contained shRNA for ITIH5 (Inter-alpha-trypsin inhibitor heavy chain 5), suggesting that ITIH5 may act as a metastasis suppressor. Consistent with this notion, metastatic PDAC cell lines had significantly lower protein expression of ITIH5 compared to immortalized pancreatic ductal epithelial cells and non-/poorly-metastatic PDAC cell lines. By manipulating expression of ITIH5 in different PDAC cell lines (over-expression in metastatic, knockdown in non-metastatic) functional and selective regulation of metastasis was observed for ITIH5. Orthotopic tumor growth of PDAC cells was not blocked following orthotopic injection. In vitro ITIH5 over-expression inhibited motility and invasion. Immunohistochemical analysis of a human PDAC tissue microarray revealed that ITIH5 expression inversely correlated with both survival and invasion/metastasis. ITIH5 is, therefore, functionally validated as a PDAC metastasis suppressor and shows promise as a prognostic biomarker.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.