ArticleInternational journal of molecular sciences2018
Exogenous Cripto-1 Suppresses Self-Renewal of Cancer Stem Cell Model.
Article in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- Hepatic drug transporters in pharmacotherapy: mechanisms, therapeutic targeting, and clinical translation.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Latest insights into the global epidemiological features, screening, early diagnosis and prognosis prediction of esophageal squamous cell carcinoma.World journal of gastroenterology · 2024Review
- TGF-β superfamily co-receptors in cancer.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Review
- Whence CRIPTO: The Reemergence of an Oncofetal Factor in 'Wounds' That Fail to Heal.International journal of molecular sciences · 2021Review
- New Insights into Cancer Targeted Therapy: Nodal and Cripto-1 as Attractive Candidates.International journal of molecular sciences · 2021Review
- Review
- A Novel Artificially Humanized Anti-Cripto-1 Antibody Suppressing Cancer Cell Growth.International journal of molecular sciences · 2021Article
- Exosomal Cripto-1 Serves as a Potential Biomarker for Perihilar Cholangiocarcinoma.Frontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cripto-1 is a glycophosphatidylinositol (GPI) anchored signaling protein of epidermal growth factor (EGF)-Cripto-1-FRL1-Cryptic (CFC) family and plays a significant role in the early developmental stages and in the different types of cancer cells, epithelial to mesenchymal transition and tumor angiogenesis. Previously, we have developed cancer stem cells (miPS-LLCcm) from mouse iPSCs by culturing them in the presence of conditioned medium of Lewis Lung Carcinoma (LLC) cells for four weeks. Nodal and Cripto-1 were confirmed to be expressed in miPS-LLCcm cells by quantitative reverse transcription PCR (rt-qPCR) implying that Cr-1 was required in maintaining stemness. To investigate the biological effect of adding exogenous soluble CR-1 to the cancer stem cells, we have prepared a C-terminally truncated soluble form of recombinant human CR-1 protein (rhsfCR-1), in which the GPI anchored moiety was removed by substitution of a stop codon through site-directed mutagenesis. rhsfCR-1 effectively suppressed the proliferation and sphere forming ability of miPS-LLCcm cells in a dose-dependent manner in the range of 0 to 5 µg/mL, due to the suppression of Nodal-Cripto-1/ALK4/Smad2 signaling pathway. Frequency of sphere-forming cells was dropped from 1/40 to 1/69 by rhsfCR-1 at 1 µg/mL. Moreover, rhsfCR-1 in the range of 0 to 1 µg/mL also limited the differentiation of miPS-LLCcm cells into vascular endothelial cells probably due to the suppression of self-renewal, which should reduce the number of cells with stemness property. As demonstrated by a soluble form of exogenous Cripto-1 in this study, the efficient blockade would be an attractive way to study Cripto-1 dependent cancer stem cell properties for therapeutic application.
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