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Article: HUNK suppresses metastasis of basal type breast cancers by disrupting the interaction between PP2A and cofilin-1

TitleHUNK suppresses metastasis of basal type breast cancers by disrupting the interaction between PP2A and cofilin-1
Authors
Issue Date2010
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2010, v. 107, n. 6, p. 2622-2627 How to Cite?
AbstractMetastasis leads to the death of most cancer patients, and basal breast cancer is the most aggressive breast tumor type. Metastasis involves a complex cell migration process dependent on cytoskeletal remodeling such that targeting such remodeling in tumor cells could be clinically beneficial. Here we show that Hormonally Upregulated Neu-associated Kinase (HUNK) is dramatically down-regulated in tumor samples and cell lines derived from basal breast cancers. Reconstitution of HUNK expression in basal breast cancer cell lines blocked actin polymerization and reduced cell motility, resulting in decreased metastases in two in vivo murine cancer models. Mechanistically, HUNK overexpression sustained the constitutive phosphorylation and inactivation of cofilin-1 (CFL-1), thereby blocking the incorporation of new actin monomers into actin filaments. HUNK reconstitution in basal breast cancer cell lines prevented protein phosphatase 2-A (PP2A), a phosphatase putatively acting on CFL-1, from binding to CFL-1. Our investigation of HUNK suggests that the interaction between PP2A and CFL-1 may be a target for antimetastasis therapy, particularly for basal breast cancers.
Persistent Identifierhttp://hdl.handle.net/10722/291945
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 3.737
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorQuintela-Fandino, Miguel-
dc.contributor.authorArpaia, Enrico-
dc.contributor.authorBrenner, Dirk-
dc.contributor.authorGoh, Theo-
dc.contributor.authorYeung, Faith Au-
dc.contributor.authorBlaser, Heiko-
dc.contributor.authorAlexandrova, Roumiana-
dc.contributor.authorLind, Evan F.-
dc.contributor.authorTusche, Mike W.-
dc.contributor.authorWakeham, Andrew-
dc.contributor.authorOhashi, Pamela S.-
dc.contributor.authorMak, Tak W.-
dc.date.accessioned2020-11-17T14:55:26Z-
dc.date.available2020-11-17T14:55:26Z-
dc.date.issued2010-
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2010, v. 107, n. 6, p. 2622-2627-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/291945-
dc.description.abstractMetastasis leads to the death of most cancer patients, and basal breast cancer is the most aggressive breast tumor type. Metastasis involves a complex cell migration process dependent on cytoskeletal remodeling such that targeting such remodeling in tumor cells could be clinically beneficial. Here we show that Hormonally Upregulated Neu-associated Kinase (HUNK) is dramatically down-regulated in tumor samples and cell lines derived from basal breast cancers. Reconstitution of HUNK expression in basal breast cancer cell lines blocked actin polymerization and reduced cell motility, resulting in decreased metastases in two in vivo murine cancer models. Mechanistically, HUNK overexpression sustained the constitutive phosphorylation and inactivation of cofilin-1 (CFL-1), thereby blocking the incorporation of new actin monomers into actin filaments. HUNK reconstitution in basal breast cancer cell lines prevented protein phosphatase 2-A (PP2A), a phosphatase putatively acting on CFL-1, from binding to CFL-1. Our investigation of HUNK suggests that the interaction between PP2A and CFL-1 may be a target for antimetastasis therapy, particularly for basal breast cancers.-
dc.languageeng-
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America-
dc.titleHUNK suppresses metastasis of basal type breast cancers by disrupting the interaction between PP2A and cofilin-1-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.0914492107-
dc.identifier.pmid20133759-
dc.identifier.pmcidPMC2823890-
dc.identifier.scopuseid_2-s2.0-77249126947-
dc.identifier.volume107-
dc.identifier.issue6-
dc.identifier.spage2622-
dc.identifier.epage2627-
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000274408100048-
dc.identifier.f10002656956-
dc.identifier.issnl0027-8424-

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