dc.contributor.author |
Singh P |
|
dc.contributor.author |
Jenkins LM |
|
dc.contributor.author |
Horst B |
|
dc.contributor.author |
Alers V |
|
dc.contributor.author |
Pradhan S |
|
dc.contributor.author |
Kaur P |
|
dc.contributor.author |
Srivastava T |
|
dc.contributor.author |
Hempel N |
|
dc.contributor.author |
Győrffy, Balázs |
|
dc.contributor.author |
Broude EV |
|
dc.contributor.author |
Lee NY |
|
dc.contributor.author |
Mythreye K |
|
dc.date.accessioned |
2019-03-20T12:41:04Z |
|
dc.date.available |
2019-03-20T12:41:04Z |
|
dc.date.issued |
2018 |
|
dc.identifier.citation |
journalVolume=78;journalIssueNumber=11;journalTitle=CANCER RESEARCH;pagerange=2978-2989;journalAbbreviatedTitle=CANCER RES; |
|
dc.identifier.uri |
http://repo.lib.semmelweis.hu//handle/123456789/6836 |
|
dc.identifier.uri |
doi:10.1158/0008-5472.CAN-17-2316 |
|
dc.description.abstract |
Inhibin is a heterodimeric TGF beta family ligand that is expressed in many cancers and is a selective biomarker for ovarian cancers; however, its tumor-specific functions remain unknown. Here, we demonstrate that the a subunit of inhibin (INHA), which is critical for the functionality of dimeric inhibin A/B, correlates with microvessel density in human ovarian tissues and is predictive of poor clinical outcomes in multiple cancers. We demonstrate that inhibin-regulated angiogenesis is necessary for metastasis. Although inhibin had no direct impact on tumor cell signaling, both tumor cell-derived and recombinant inhibin elicit a strong paracrine response from endothelial cells by triggering SMAD1/5 activation and angiogenesis in vitro and in vivo. Inhibin-induced angiogenesis was abrogated via anti-inhibin a antibodies. The endothelial-specific TGF beta receptor complex comprising ALK1 and endoglin was a crucial mediator of inhibin signaling, offering a molecular mechanism for inhibin-mediated angiogenesis. These results are the first to define a role for inhibin in tumor metastasis and vascularization and offer an antibody-based approach for targeting inhibin therapeutically. Significance: Inhibin is a predictor of poor patient survival in multiple cancers and is a potential target for antiangiogenic therapies. (C) 2018 AACR. |
|
dc.format.extent |
2978-2989 |
|
dc.relation.ispartof |
urn:issn:0008-5472 |
|
dc.title |
Inhibin Is a Novel Paracrine Factor for Tumor Angiogenesis and Metastasis |
|
dc.type |
Journal Article |
|
dc.date.updated |
2019-03-06T09:04:05Z |
|
dc.language.rfc3066 |
en |
|
dc.rights.holder |
NULL |
|
dc.identifier.mtmt |
3408797 |
|
dc.identifier.wos |
000433930700017 |
|
dc.identifier.pubmed |
29535220 |
|
dc.contributor.department |
SE/AOK/K/II. Sz. Gyermekgyógyászati Klinika |
|
dc.contributor.department |
MTA TTK/Enzimológiai Intézet |
|
dc.contributor.department |
MTA TTK/EI/Onkológiai Biomarker Kutatócsoport (Lendület) |
|
dc.contributor.institution |
Semmelweis Egyetem |
|
dc.contributor.institution |
Enzimológiai Intézet |
|