Kizilboga T, Baskale EA, Yildiz J, et al. - Researchers here studied Bag-1 expression profiles in tumor and normal tissues of breast cancer patients with different receptor status in order to delineate the effects of Bag-1 on major cell survival pathways associated with breast cancer. Overexpression of Bag-1 was observed in breast tumors in all molecular subtypes, ie, regardless of their ER, PR and Her2 expression profile. In breast cancer cell lines, ectopic expression of Bag-1 led to the activation of B-Raf, C-Raf and Akt kinases, which are also upregulated in breast tumors. With B-Raf, C-Raf and Akt, Bag-1 forms complexes in breast cancer cells, heightening their phosphorylation and activation and finally resulting in phosphorylation of the pro-apoptotic Bad protein at Ser112 and Ser136. This leads to the re-localization of Bad to the nucleus and inhibits apoptosis in favor of cell survival. Findings indicate that breast cancer cells exploit Bad inhibition by Bag-1 through activation of Raf and Akt kinases as effective survival and growth strategy. This suggests the potential of targeting the molecular interactions between Bag-1 and these kinases as an effective anticancer therapy.