TIMP-1 mediates TGF-beta-dependent crosstalk between hepatic stellate and cancer cells via FAK signaling
DC Field | Value | Language |
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dc.contributor.author | Park, Sang-A | - |
dc.contributor.author | Kim, Min-Jin | - |
dc.contributor.author | Park, So-Yeon | - |
dc.contributor.author | Kim, Jung-Shin | - |
dc.contributor.author | Lim, Woosung | - |
dc.contributor.author | Nam, Jeong-Seok | - |
dc.contributor.author | Sheen, Yhun Yhong | - |
dc.date.available | 2020-02-28T07:42:43Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2015-11-09 | - |
dc.identifier.issn | 2045-2322 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/9913 | - |
dc.description.abstract | Transforming growth factor-beta (TGF-beta) signaling plays a key role in progression and metastasis of HCC. This study was undertaken to gain the proof of concept of a small-molecule inhibitor of TGF-beta type I receptor kinase, EW-7197 as a potent anti-cancer therapy for HCC. We identified tissue inhibitors of metalloproteinases-1 (TIMP-1) as one of the secreted proteins of hepatic stellate cells (HSCs) and a key mediator of TGF-beta-mediated crosstalk between HSCs and HCC cells. TGF-beta signaling led to increased expression of TIMP-1, which activates focal adhesion kinase (FAK) signaling via its interaction with CD63. Inhibition of TGF-beta signaling using EW-7197 significantly attenuated the progression and intrahepatic metastasis of HCC in an SK-HEP1-Luc orthotopic-xenograft mouse model. In addition, EW-7197 inhibited TGF-beta-stimulated TIMP-1 secretion by HSCs as well as the TIMP-1-induced proliferation, motility, and survival of HCC cells. Further, EW-7197 interrupted TGF-beta-mediated epithelial-to-mesenchymal transition and Akt signaling, leading to significant reductions in the motility and anchorage-independent growth of HCC cells. In conclusion, we found that TIMP-1 mediates TGF-beta-regulated crosstalk between HSCs and HCC cells via FAK signaling. In addition, EW-7197 demonstrates potent in vivo anti-cancer therapeutic activity and may be a potential new anticancer drug of choice to treat patients with liver cancer. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.relation.isPartOf | SCIENTIFIC REPORTS | - |
dc.subject | BREAST EPITHELIAL-CELLS | - |
dc.subject | HUMAN HEPATOCELLULAR-CARCINOMA | - |
dc.subject | GROWTH-FACTOR | - |
dc.subject | TISSUE INHIBITOR | - |
dc.subject | MESENCHYMAL TRANSITION | - |
dc.subject | METALLOPROTEINASE-1 | - |
dc.subject | STROMA | - |
dc.subject | LIVER | - |
dc.subject | METASTASIS | - |
dc.subject | RECEPTOR | - |
dc.title | TIMP-1 mediates TGF-beta-dependent crosstalk between hepatic stellate and cancer cells via FAK signaling | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000364299300001 | - |
dc.identifier.doi | 10.1038/srep16492 | - |
dc.identifier.bibliographicCitation | SCIENTIFIC REPORTS, v.5 | - |
dc.identifier.scopusid | 2-s2.0-84946762673 | - |
dc.citation.title | SCIENTIFIC REPORTS | - |
dc.citation.volume | 5 | - |
dc.contributor.affiliatedAuthor | Nam, Jeong-Seok | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | BREAST EPITHELIAL-CELLS | - |
dc.subject.keywordPlus | HUMAN HEPATOCELLULAR-CARCINOMA | - |
dc.subject.keywordPlus | GROWTH-FACTOR | - |
dc.subject.keywordPlus | TISSUE INHIBITOR | - |
dc.subject.keywordPlus | MESENCHYMAL TRANSITION | - |
dc.subject.keywordPlus | METALLOPROTEINASE-1 | - |
dc.subject.keywordPlus | STROMA | - |
dc.subject.keywordPlus | LIVER | - |
dc.subject.keywordPlus | METASTASIS | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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