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dc.contributor.authorZohrap, N.en_US
dc.contributor.authorSaatci, Ö.en_US
dc.contributor.authorOzes, B.en_US
dc.contributor.authorCoban, I.en_US
dc.contributor.authorAtay, H. M.en_US
dc.contributor.authorBattaloglu, E.en_US
dc.contributor.authorŞahin, Ö.en_US
dc.contributor.authorBugra, K.en_US
dc.date.accessioned2019-02-21T16:08:20Zen_US
dc.date.available2019-02-21T16:08:20Zen_US
dc.date.issued2018en_US
dc.identifier.urihttp://hdl.handle.net/11693/50409en_US
dc.description.abstractSalt Inducible Kinase2 (SIK2) has been shown to contribute to tumorigenesis in multiple tumor types in a dichotomous manner. However, little is known about its contribution to breast malignancies. Here, we report SIK2 as a potential tumor suppressor in breast cancer whose expression was reduced in tumor tissues and breast cancer cell lines compared to normal counterparts. In vitro loss- and gainof- function experiments combined with xenograft studies demonstrated that SIK2- mediated attenuation of proliferation and survival of breast cancer cells with parallel inhibition of both Ras/Erk and PI3K/Akt pathways. Our findings elucidated that SIK2 has also an inhibitory role in migration/invasion ability of breast cancer cells through regulation of epithelial mesenchymal transition. Immunostaining of patient tumors revealed that SIK2 protein level is frequently downregulated in invasive mammary carcinomas and negatively correlated with the mitotic activity of the cells in triple negative breast cancers and hormone positive tumors. Strikingly, patient survival analysis indicated that higher levels of SIK2 are significantly associated with better survival, especially in basal breast cancer cases. Overall, our findings suggest SIK2 as a potential tumor suppressor in the control of breast tumorigenesis, at least in part, via inhibiting PI3K/Akt and Ras/ERK signaling cascades simultaneously and a novel prognostic marker, especially in basal subtypes of breast cancer.en_US
dc.language.isoEnglishen_US
dc.source.titleOncotargeten_US
dc.relation.isversionofhttps://doi.org/10.18632/oncotarget.25082en_US
dc.subjectBreast canceren_US
dc.subjectEMTen_US
dc.subjectRas/ERK and PI3K/Akt signalingen_US
dc.subjectSIK2en_US
dc.subjectTumor suppressoren_US
dc.titleSIK2 attenuates proliferation and survival of breast cancer cells with simultaneous perturbation of MAPK and PI3K/Akt pathwaysen_US
dc.typeArticleen_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.citation.spage21876en_US
dc.citation.epage21892en_US
dc.citation.volumeNumber9en_US
dc.citation.issueNumber31en_US
dc.identifier.doi10.18632/oncotarget.25082en_US
dc.publisherImpact Journals LLCen_US
dc.identifier.eissn1949-2553


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