ArticleBMC cancer2019
Bag-1 stimulates Bad phosphorylation through activation of Akt and Raf kinases to mediate cell survival in breast cancer.
Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 34 citations in OpenAlex.
- Genetic Variants in HSP70 Family and BAG Co-Chaperone Genes: Associations with Coronary Artery Disease Risk and Potential Regulatory Effects.International journal of molecular sciences · 2026Article
- Shu Gan Jie Yu herbal combination enhances tamoxifen sensitivity in breast cancer cells via modulation of the SNCG/Frontiers in pharmacology · 2026Article
- Oxidative stress and antioxidants in breast cancer: a double-edged sword.Frontiers in oncology · 2026Review
- Review
- Targeting mTORC1 to promote ferroptosis and apoptosis in endometrial cancer with PI3K-Akt-mTOR pathway mutation.Ferroptosis and oxidative stress · 2025Article
- Modulation ofPeerJ · 2025Article
- Bag-1-mediated HSF1 phosphorylation regulates expression of heat shock proteins in breast cancer cells.FEBS open bio · 2024Article
- Pitavastatin sensitizes the EGFR-TKI associated resistance in lung cancer by inhibiting YAP/AKT/BAD-BCL-2 pathway.Cancer cell international · 2024Article
- Vertical pathway inhibition of receptor tyrosine kinases and BAD with synergistic efficacy in triple negative breast cancer.NPJ precision oncology · 2024Article
- Predictive, preventive, and personalized medicine in breast cancer: targeting the PI3K pathway.Journal of translational medicine · 2024Review
- Kinase signalling adaptation supports dysfunctional mitochondria in disease.Frontiers in molecular biosciences · 2024Review
- PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer.Molecular cancer · 2023Review
- Bag-1 Protects Nucleus Pulposus Cells from Oxidative Stress by Interacting with HSP70.Biomedicines · 2023Article
- Bioactive PI3-kinase/Akt/mTOR Inhibitors in Targeted Lung Cancer Therapy.Advanced pharmaceutical bulletin · 2023Review
- A chemical probe for BAG1 targets androgen receptor-positive prostate cancer through oxidative stress signaling pathway.iScience · 2022Article
- Polyphenols: Chemoprevention and therapeutic potentials in hematological malignancies.Frontiers in nutrition · 2022Review
- Article
- The comparison of differentially expressed microRNAs in Bag-1 deficient and wild type MCF-7 breast cancer cells by small RNA sequencing.Turkish journal of biology = Turk biyoloji dergisi · 2022Article
- Sepsis induces muscle atrophy by inhibiting proliferation and promoting apoptosis via PLK1-AKT signalling.Journal of cellular and molecular medicine · 2021Article
- Co-Chaperone Bag-1 Plays a Role in the Autophagy-Dependent Cell Survival through Beclin 1 Interaction.Molecules (Basel, Switzerland) · 2021Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundBag-1 (Bcl-2-associated athanogene) is a multifunctional anti-apoptotic protein frequently overexpressed in cancer. Bag-1 interacts with a variety of cellular targets including Hsp70/Hsc70 chaperones, Bcl-2, nuclear hormone receptors, Akt and Raf kinases. In this study, we investigated in detail the effects of Bag-1 on major cell survival pathways associated with breast cancer.
methodsUsing immunoblot analysis, we examined Bag-1 expression profiles in tumor and normal tissues of breast cancer patients with different receptor status. We investigated the effects of Bag-1 on cell proliferation, apoptosis, Akt and Raf kinase pathways, and Bad phosphorylation by implementing ectopic expression or knockdown of Bag-1 in MCF-7, BT-474, MDA-MB-231 and MCF-10A breast cell lines. We also tested these in tumor and normal tissues from breast cancer patients. We investigated the interactions between Bag-1, Akt and Raf kinases in cell lines and tumor tissues by co-immunoprecipitation, and their subcellular localization by immunocytochemistry and immunohistochemistry.
resultsWe observed that Bag-1 is overexpressed in breast tumors in all molecular subtypes, i.e., regardless of their ER, PR and Her2 expression profile. Ectopic expression of Bag-1 in breast cancer cell lines results in the activation of B-Raf, C-Raf and Akt kinases, which are also upregulated in breast tumors. Bag-1 forms complexes with B-Raf, C-Raf and Akt in breast cancer cells, enhancing their phosphorylation and activation, and ultimately leading to phosphorylation of the pro-apoptotic Bad protein at Ser112 and Ser136. This causes Bad's re-localization to the nucleus, and inhibits apoptosis in favor of cell survival.
conclusionsOverall, Bad inhibition by Bag-1 through activation of Raf and Akt kinases is an effective survival and growth strategy exploited by breast cancer cells. Therefore, targeting the molecular interactions between Bag-1 and these kinases might prove an effective anticancer therapy.
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