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Article: Inactivating mutations and X-ray crystal structure of the tumor suppressor OPCML reveal cancer-associated functions

TitleInactivating mutations and X-ray crystal structure of the tumor suppressor OPCML reveal cancer-associated functions
Authors
Issue Date2019
Citation
Nature Communications, 2019, v. 10, n. 1, article no. 3134 How to Cite?
AbstractOPCML, a tumor suppressor gene, is frequently silenced epigenetically in ovarian and other cancers. Here we report, by analysis of databases of tumor sequences, the observation of OPCML somatic missense mutations from various tumor types and the impact of these mutations on OPCML function, by solving the X-ray crystal structure of this glycoprotein to 2.65 Å resolution. OPCML consists of an extended arrangement of three immunoglobulin-like domains and homodimerizes via a network of contacts between membrane-distal domains. We report the generation of a panel of OPCML variants with representative clinical mutations and demonstrate clear phenotypic effects in vitro and in vivo including changes to anchorage-independent growth, interaction with activated cognate receptor tyrosine kinases, cellular migration, invasion in vitro and tumor growth in vivo. Our results suggest that clinically occurring somatic missense mutations in OPCML have the potential to contribute to tumorigenesis in a variety of cancers.
Persistent Identifierhttp://hdl.handle.net/10722/341492
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorBirtley, James R.-
dc.contributor.authorAlomary, Mohammad-
dc.contributor.authorZanini, Elisa-
dc.contributor.authorAntony, Jane-
dc.contributor.authorMaben, Zachary-
dc.contributor.authorWeaver, Grant C.-
dc.contributor.authorVon Arx, Claudia-
dc.contributor.authorMura, Manuela-
dc.contributor.authorMarinho, Aline T.-
dc.contributor.authorLu, Haonan-
dc.contributor.authorMorecroft, Eloise V.N.-
dc.contributor.authorKarali, Evdoxia-
dc.contributor.authorChayen, Naomi E.-
dc.contributor.authorTate, Edward W.-
dc.contributor.authorJurewicz, Mollie-
dc.contributor.authorStern, Lawrence J.-
dc.contributor.authorRecchi, Chiara-
dc.contributor.authorGabra, Hani-
dc.date.accessioned2024-03-13T08:43:13Z-
dc.date.available2024-03-13T08:43:13Z-
dc.date.issued2019-
dc.identifier.citationNature Communications, 2019, v. 10, n. 1, article no. 3134-
dc.identifier.urihttp://hdl.handle.net/10722/341492-
dc.description.abstractOPCML, a tumor suppressor gene, is frequently silenced epigenetically in ovarian and other cancers. Here we report, by analysis of databases of tumor sequences, the observation of OPCML somatic missense mutations from various tumor types and the impact of these mutations on OPCML function, by solving the X-ray crystal structure of this glycoprotein to 2.65 Å resolution. OPCML consists of an extended arrangement of three immunoglobulin-like domains and homodimerizes via a network of contacts between membrane-distal domains. We report the generation of a panel of OPCML variants with representative clinical mutations and demonstrate clear phenotypic effects in vitro and in vivo including changes to anchorage-independent growth, interaction with activated cognate receptor tyrosine kinases, cellular migration, invasion in vitro and tumor growth in vivo. Our results suggest that clinically occurring somatic missense mutations in OPCML have the potential to contribute to tumorigenesis in a variety of cancers.-
dc.languageeng-
dc.relation.ispartofNature Communications-
dc.titleInactivating mutations and X-ray crystal structure of the tumor suppressor OPCML reveal cancer-associated functions-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/s41467-019-10966-8-
dc.identifier.pmid31316070-
dc.identifier.scopuseid_2-s2.0-85069512251-
dc.identifier.volume10-
dc.identifier.issue1-
dc.identifier.spagearticle no. 3134-
dc.identifier.epagearticle no. 3134-
dc.identifier.eissn2041-1723-
dc.identifier.isiWOS:000475833500001-

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