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

SIK2 attenuates proliferation and survival of breast cancer cells with simultaneous perturbation of MAPK and PI3K/Akt pathways. Oncotarget. 2018 Apr 24;9(31):21876-21892 Authors: Zohrap N, Saatci Ö, Ozes B, Coban I, Atay HM, Battaloglu E, Şahin Ö, Bugra K 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 br...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research