Publicação
Collagen-rich omentum is a premetastatic niche for integrin a2-mediated peritoneal metastasis
| Resumo: | The extracellular matrix (ECM) plays critical roles in tumor progression and metastasis. However, the contribution of ECM proteins to early metastatic onset in the peritoneal cavity remains unexplored. Here, we suggest a new route of metastasis through the interaction of integrin alpha 2 (ITGA2) with collagens enriched in the tumor coinciding with poor outcome in patients with ovarian cancer. Using multiple gene-edited cell lines and patient-derived samples, we demonstrate that ITGA2 triggers cancer cell adhesion to collagen, promotes cell migration, anoikis resistance, mesothelial clearance, and peritoneal metastasis in vitro and in vivo. Mechanistically, phosphoproteomics identify an ITGA2-dependent phosphorylation of focal adhesion kinase and mitogen-activated protein kinase pathway leading to enhanced oncogenic properties. Consequently, specific inhibition of ITGA2-mediated cancer cell-collagen interaction or targeting focal adhesion signaling may present an opportunity for therapeutic intervention of metastatic spread in ovarian cancer. |
|---|---|
| Autores principais: | Huang, YL |
| Outros Autores: | Liang, CY; Ritz, D; Coelho, R; Septiadi, D; Estermann, M; Cumin, C; Rimmer, N; Schötzau, A; López, MN; Fedier, A; Konantz, M; Vlajnic, T; Calabrese, D; Lengerke, C; David, L; Rothen-Rutishauser, B; Jacob, F; Heinzelmann-Schwarz, V |
| Assunto: | Cell adhesion Collagen Peritoneal metastasis Cancer biology Cell biology Focal adhesion kinase Human Integrin alpah 2 Mouse Omentum Zebrafish |
| Ano: | 2020 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Porto |
| Idioma: | inglês |
| Origem: | Repositório Aberto da Universidade do Porto |
| _version_ | 1867767306977804288 |
|---|---|
| author | Huang, YL |
| author2 | Liang, CY Ritz, D Coelho, R Septiadi, D Estermann, M Cumin, C Rimmer, N Schötzau, A López, MN Fedier, A Konantz, M Vlajnic, T Calabrese, D Lengerke, C David, L Rothen-Rutishauser, B Jacob, F Heinzelmann-Schwarz, V |
| author2_role | author author author author author author author author author author author author author author author author author author |
| author_facet | Huang, YL Liang, CY Ritz, D Coelho, R Septiadi, D Estermann, M Cumin, C Rimmer, N Schötzau, A López, MN Fedier, A Konantz, M Vlajnic, T Calabrese, D Lengerke, C David, L Rothen-Rutishauser, B Jacob, F Heinzelmann-Schwarz, V |
| author_role | author |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Huang, YL\"},{\"Person.name\":\"Liang, CY\"},{\"Person.name\":\"Ritz, D\"},{\"Person.name\":\"Coelho, R\"},{\"Person.name\":\"Septiadi, D\"},{\"Person.name\":\"Estermann, M\"},{\"Person.name\":\"Cumin, C\"},{\"Person.name\":\"Rimmer, N\"},{\"Person.name\":\"Schötzau, A\"},{\"Person.name\":\"López, MN\"},{\"Person.name\":\"Fedier, A\"},{\"Person.name\":\"Konantz, M\"},{\"Person.name\":\"Vlajnic, T\"},{\"Person.name\":\"Calabrese, D\"},{\"Person.name\":\"Lengerke, C\"},{\"Person.name\":\"David, L\"},{\"Person.name\":\"Rothen-Rutishauser, B\"},{\"Person.name\":\"Jacob, F\"},{\"Person.name\":\"Heinzelmann-Schwarz, V\"}] |
| datacite.creators.creator.creatorName.fl_str_mv | Huang, YL Liang, CY Ritz, D Coelho, R Septiadi, D Estermann, M Cumin, C Rimmer, N Schötzau, A López, MN Fedier, A Konantz, M Vlajnic, T Calabrese, D Lengerke, C David, L Rothen-Rutishauser, B Jacob, F Heinzelmann-Schwarz, V |
| datacite.date.Accepted.fl_str_mv | 2020-01-01T00:00:00Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Cell adhesion Collagen Peritoneal metastasis Cancer biology Cell biology Focal adhesion kinase Human Integrin alpah 2 Mouse Omentum Zebrafish |
| datacite.titles.title.fl_str_mv | Collagen-rich omentum is a premetastatic niche for integrin a2-mediated peritoneal metastasis |
| dc.creator.none.fl_str_mv | Huang, YL Liang, CY Ritz, D Coelho, R Septiadi, D Estermann, M Cumin, C Rimmer, N Schötzau, A López, MN Fedier, A Konantz, M Vlajnic, T Calabrese, D Lengerke, C David, L Rothen-Rutishauser, B Jacob, F Heinzelmann-Schwarz, V |
| dc.date.Accepted.fl_str_mv | 2020-01-01T00:00:00Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/10216/143479 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | eLife Sciences Publications |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Cell adhesion Collagen Peritoneal metastasis Cancer biology Cell biology Focal adhesion kinase Human Integrin alpah 2 Mouse Omentum Zebrafish |
| dc.title.fl_str_mv | Collagen-rich omentum is a premetastatic niche for integrin a2-mediated peritoneal metastasis |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | The extracellular matrix (ECM) plays critical roles in tumor progression and metastasis. However, the contribution of ECM proteins to early metastatic onset in the peritoneal cavity remains unexplored. Here, we suggest a new route of metastasis through the interaction of integrin alpha 2 (ITGA2) with collagens enriched in the tumor coinciding with poor outcome in patients with ovarian cancer. Using multiple gene-edited cell lines and patient-derived samples, we demonstrate that ITGA2 triggers cancer cell adhesion to collagen, promotes cell migration, anoikis resistance, mesothelial clearance, and peritoneal metastasis in vitro and in vivo. Mechanistically, phosphoproteomics identify an ITGA2-dependent phosphorylation of focal adhesion kinase and mitogen-activated protein kinase pathway leading to enhanced oncogenic properties. Consequently, specific inhibition of ITGA2-mediated cancer cell-collagen interaction or targeting focal adhesion signaling may present an opportunity for therapeutic intervention of metastatic spread in ovarian cancer. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| id | rabertoup_32c1fa59cc8c00a2d0b2df855fbe7325 |
| identifier.url.fl_str_mv | https://hdl.handle.net/10216/143479 |
| instacron_str | UP |
| institution | Universidade do Porto |
| instname_str | Universidade do Porto |
| language | eng |
| network_acronym_str | rabertoup |
| network_name_str | Repositório Aberto da Universidade do Porto |
| oai_identifier_str | oai:repositorio-aberto.up.pt:10216/143479 |
| organization_str_mv | urn:organizationAcronym:up |
| person_str_mv | Huang, YL Liang, CY Ritz, D Coelho, R Septiadi, D Estermann, M Cumin, C Rimmer, N Schötzau, A López, MN Fedier, A Konantz, M Vlajnic, T Calabrese, D Lengerke, C David, L Rothen-Rutishauser, B Jacob, F Heinzelmann-Schwarz, V |
| publishDate | 2020 |
| publisher.none.fl_str_mv | eLife Sciences Publications |
| reponame_str | Repositório Aberto da Universidade do Porto |
| repository_id_str | urn:repositoryAcronym:rabertoup |
| service_str_mv | urn:repositoryAcronym:rabertoup |
| spelling | The extracellular matrix (ECM) plays critical roles in tumor progression and metastasis. However, the contribution of ECM proteins to early metastatic onset in the peritoneal cavity remains unexplored. Here, we suggest a new route of metastasis through the interaction of integrin alpha 2 (ITGA2) with collagens enriched in the tumor coinciding with poor outcome in patients with ovarian cancer. Using multiple gene-edited cell lines and patient-derived samples, we demonstrate that ITGA2 triggers cancer cell adhesion to collagen, promotes cell migration, anoikis resistance, mesothelial clearance, and peritoneal metastasis in vitro and in vivo. Mechanistically, phosphoproteomics identify an ITGA2-dependent phosphorylation of focal adhesion kinase and mitogen-activated protein kinase pathway leading to enhanced oncogenic properties. Consequently, specific inhibition of ITGA2-mediated cancer cell-collagen interaction or targeting focal adhesion signaling may present an opportunity for therapeutic intervention of metastatic spread in ovarian cancer.application/pdfengeLife Sciences PublicationsCollagen-rich omentum is a premetastatic niche for integrin a2-mediated peritoneal metastasisHuang, YLLiang, CYRitz, DCoelho, RSeptiadi, DEstermann, MCumin, CRimmer, NSchötzau, ALópez, MNFedier, AKonantz, MVlajnic, TCalabrese, DLengerke, CDavid, LRothen-Rutishauser, BJacob, FHeinzelmann-Schwarz, VHandlehttps://hdl.handle.net/10216/143479ISSNIsPartOf2050-084XDOIIsPartOf10.7554/eLife.5944220202020-01-01T00:00:00Zhttp://purl.org/coar/access_right/c_abf2open accessCell adhesionCollagenPeritoneal metastasisCancer biologyCell biologyFocal adhesion kinaseHumanIntegrin alpah 2MouseOmentumZebrafish5548743 byteshttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorio-aberto.up.pt/bitstream/10216/143479/1/10.7554-eLife.59442.pdfliteraturehttp://purl.org/coar/resource_type/c_6501journal article |
| spellingShingle | Collagen-rich omentum is a premetastatic niche for integrin a2-mediated peritoneal metastasis Huang, YL Cell adhesion Collagen Peritoneal metastasis Cancer biology Cell biology Focal adhesion kinase Human Integrin alpah 2 Mouse Omentum Zebrafish |
| status | SINGLETON |
| subject.fl_str_mv | Cell adhesion Collagen Peritoneal metastasis Cancer biology Cell biology Focal adhesion kinase Human Integrin alpah 2 Mouse Omentum Zebrafish |
| title | Collagen-rich omentum is a premetastatic niche for integrin a2-mediated peritoneal metastasis |
| title_full | Collagen-rich omentum is a premetastatic niche for integrin a2-mediated peritoneal metastasis |
| title_fullStr | Collagen-rich omentum is a premetastatic niche for integrin a2-mediated peritoneal metastasis |
| title_full_unstemmed | Collagen-rich omentum is a premetastatic niche for integrin a2-mediated peritoneal metastasis |
| title_short | Collagen-rich omentum is a premetastatic niche for integrin a2-mediated peritoneal metastasis |
| title_sort | Collagen-rich omentum is a premetastatic niche for integrin a2-mediated peritoneal metastasis |
| topic | Cell adhesion Collagen Peritoneal metastasis Cancer biology Cell biology Focal adhesion kinase Human Integrin alpah 2 Mouse Omentum Zebrafish |
| topic_facet | Cell adhesion Collagen Peritoneal metastasis Cancer biology Cell biology Focal adhesion kinase Human Integrin alpah 2 Mouse Omentum Zebrafish |
| url | https://hdl.handle.net/10216/143479 |
| visible | 1 |