SIK2 attenuates proliferation and survival of breast cancer cells with simultaneous perturbation of MAPK and PI3K/Akt pathways

Oncotarget
Neslihan ZohrapKuyas Bugra

Abstract

Salt 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 gain-of-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...Continue Reading

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Citations

Aug 14, 2020·Signal Transduction and Targeted Therapy·Zicheng SunJianping Guo
Sep 8, 2021·Environmental Toxicology·Yuan LiChunrong Dong

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Datasets Mentioned

BETA
GSE53752
GSE21653

Methods Mentioned

BETA
xenograft
transfection
xenografts
transfections
PCR

Software Mentioned

Adobe Photoshop
BioRAD IQ5
LAF
GraphPad

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AKT Pathway

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