The heparan sulfate proteoglycan syndecan‐1 regulates colon cancer stem cell function via a focal adhesion kinase—Wnt signaling axis
| العنوان: | The heparan sulfate proteoglycan syndecan‐1 regulates colon cancer stem cell function via a focal adhesion kinase—Wnt signaling axis |
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| المؤلفون: | Valeria Tria, Rolland Reinbold, George W. Yip, Wey-Cheng Sim, Sherif Abdelaziz Ibrahim, Ileana Zucchi, Burkhard Greve, Sampath Kumar Katakam, Theodoros Karnavas, Martin Götte, Stefano Molgora, Paride Pelucchi, Eleonora Piscitelli, Eslam A. El-Ghonaimy |
| المصدر: | The FEBS Journal The FEBS journal (2020). doi:10.1111/febs.15356 info:cnr-pdr/source/autori:Katakam, Sampath Kumar; Tria, Valeria; Sim, Wey-Cheng; Yip, George W.; Molgora, Stefano; Karnavas, Theodoros; Elghonaimy, Eslam A.; Pelucchi, Paride; Piscitelli, Eleonora; Ibrahim, Sherif Abdelaziz; Zucchi, Ileana; Reinbold, Rolland; Greve, Burkhard; Goette, Martin/titolo:The heparan sulfate proteoglycan syndecan-1 regulates colon cancer stem cell function via a focal adhesion kinase-Wnt signaling axis/doi:10.1111%2Ffebs.15356/rivista:The FEBS journal (Print)/anno:2020/pagina_da:/pagina_a:/intervallo_pagine:/volume |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Indoles, Biochemistry, Receptors, G-Protein-Coupled, Syndecan 1, Mice, 0302 clinical medicine, Cell Movement, AC133 Antigen, RNA, Small Interfering, Wnt Signaling Pathway, Sulfonamides, biology, Chemistry, Integrin beta1, Wnt signaling pathway, LGR5, Nanog Homeobox Protein, Epithelial Cell Adhesion Molecule, Tumor Burden, 3. Good health, Cell biology, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Colonic Neoplasms, Neoplastic Stem Cells, Stem cell, HT29 Cells, Oligopeptides, Transcription Factor 7-Like 2 Protein, Homeobox protein NANOG, extracellular matrix, Integrin, Kruppel-Like Transcription Factors, tumor-initiating cells, Aldehyde Dehydrogenase 1 Family, Focal adhesion, 03 medical and health sciences, Cancer stem cell, Spheroids, Cellular, glycosaminoglycan, Animals, Humans, Benzothiazoles, xenograft, Molecular Biology, Cell Proliferation, Cell Biology, syndecans, Xenograft Model Antitumor Assays, Sex-Determining Region Y Protein, 030104 developmental biology, Focal Adhesion Kinase 1, biology.protein, Syndecan-1, Caco-2 Cells |
| الوصف: | In colon cancer, downregulation of the transmembrane heparan sulfate proteoglycan syndecan-1 (Sdc-1) is associated with increased invasiveness, metastasis, and dedifferentiation. As Sdc-1 modulates signaling pathways relevant to stem cell function, we tested the hypothesis that it may regulate a tumor-initiating cell phenotype. Sdc-1 small-interfering RNA knockdown in the human colon cancer cell lines Caco2 and HT-29 resulted in an increased side population (SP), enhanced aldehyde dehydrogenase 1 activity, and higher expression of CD133, LGR5, EPCAM, NANOG, SRY (sex-determining region Y)-box 2, KLF2, and TCF4/TCF7L2. Sdc-1 knockdown enhanced sphere formation, cell viability, Matrigel invasiveness, and epithelial-to-mesenchymal transition-related gene expression. Sdc-1-depleted HT-29 xenograft growth was increased compared to controls. Decreased Sdc-1 expression was associated with an increased activation of β1-integrins, focal adhesion kinase (FAK), and wingless-type (Wnt) signaling. Pharmacological FAK and Wnt inhibition blocked the enhanced stem cell phenotype and invasive growth. Sequential flow cytometric SP enrichment substantially enhanced the stem cell phenotype of Sdc-1-depleted cells, which showed increased resistance to doxorubicin chemotherapy and irradiation. In conclusion, Sdc-1 depletion cooperatively enhances activation of integrins and FAK, which then generates signals for increased invasiveness and cancer stem cell properties. Our findings may provide a novel concept to target a stemness-associated signaling axis as a therapeutic strategy to reduce metastatic spread and cancer recurrence. DATABASES: The GEO accession number of the Affymetrix transcriptomic screening is GSE58751. |
| تدمد: | 1742-4658 1742-464X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c8ea4b24fab851ea7f018baf542f61c0Test https://doi.org/10.1111/febs.15356Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c8ea4b24fab851ea7f018baf542f61c0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17424658 1742464X |
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