Search: onr:"swepub:oai:DiVA.org:uu-339268" > Overactivation of t...
Fältnamn | Indikatorer | Metadata |
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000 | 03748naa a2200421 4500 | |
001 | oai:DiVA.org:uu-339268 | |
003 | SwePub | |
008 | 180117s2013 | |||||||||||000 ||eng| | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3392682 URI |
024 | 7 | a https://doi.org/10.1002/hep.265972 DOI |
040 | a (SwePub)uu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Bertran, Esther4 aut |
245 | 1 0 | a Overactivation of the TGF-β pathway confers a mesenchymal-like phenotype and CXCR4-dependent migratory properties to liver tumor cells |
264 | c 2013-10-11 | |
264 | 1 | b Ovid Technologies (Wolters Kluwer Health),c 2013 |
338 | a print2 rdacarrier | |
520 | a UNLABELLED: Transforming growth factor-beta (TGF-β) is an important regulatory suppressor factor in hepatocytes. However, liver tumor cells develop mechanisms to overcome its suppressor effects and respond to this cytokine by inducing other processes, such as the epithelial-mesenchymal transition (EMT), which contributes to tumor progression and dissemination. Recent studies have placed chemokines and their receptors at the center not only of physiological cell migration but also of pathological processes, such as metastasis in cancer. In particular, CXCR4 and its ligand, stromal cell-derived factor 1α (SDF-1α) / chemokine (C-X-C motif) ligand 12 (CXCL12) have been revealed as regulatory molecules involved in the spreading and progression of a variety of tumors. Here we show that autocrine stimulation of TGF-β in human liver tumor cells correlates with a mesenchymal-like phenotype, resistance to TGF-β-induced suppressor effects, and high expression of CXCR4, which is required for TGF-β-induced cell migration. Silencing of the TGF-β receptor1 (TGFBR1), or its specific inhibition, recovered the epithelial phenotype and attenuated CXCR4 expression, inhibiting cell migratory capacity. In an experimental mouse model of hepatocarcinogenesis (diethylnitrosamine-induced), tumors showed increased activation of the TGF-β pathway and enhanced CXCR4 levels. In human hepatocellular carcinoma tumors, high levels of CXCR4 always correlated with activation of the TGF-β pathway, a less differentiated phenotype, and a cirrhotic background. CXCR4 concentrated at the tumor border and perivascular areas, suggesting its potential involvement in tumor cell dissemination.CONCLUSION: A crosstalk exists among the TGF-β and CXCR4 pathways in liver tumors, reflecting a novel molecular mechanism that explains the protumorigenic effects of TGF-β and opens new perspectives for tumor therapy. | |
650 | 7 | a NATURVETENSKAPx Biologi0 (SwePub)1062 hsv//swe |
650 | 7 | a NATURAL SCIENCESx Biological Sciences0 (SwePub)1062 hsv//eng |
700 | 1 | a Crosas-Molist, Eva4 aut |
700 | 1 | a Sancho, Patricia4 aut |
700 | 1 | a Caja, Laiau Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain4 aut0 (Swepub:uu)laica659 |
700 | 1 | a Lopez-Luque, Judit4 aut |
700 | 1 | a Navarro, Estanislao4 aut |
700 | 1 | a Egea, Gustavo4 aut |
700 | 1 | a Lastra, Raquel4 aut |
700 | 1 | a Serrano, Teresa4 aut |
700 | 1 | a Ramos, Emilio4 aut |
700 | 1 | a Fabregat, Isabel4 aut |
710 | 2 | a Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain4 org |
773 | 0 | t Hepatologyd : Ovid Technologies (Wolters Kluwer Health)g 58:6, s. 2032-44q 58:6<2032-44x 0270-9139x 1527-3350 |
856 | 4 | u https://aasldpubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hep.26597 |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-339268 |
856 | 4 8 | u https://doi.org/10.1002/hep.26597 |
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