mProX™ Human PDK1 Stable Cell Line

Gunaydin, Burcu. et al. "Cytotoxic effects of Phenformin on ovarian cancer cells: expression of HIF-1α and PDK1 in the hypoxic microenvironment." Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie, 2023.
Currently, numerous anticancer medications find clinical application in the context of ovarian cancer, a major contributor to cancer-related fatalities in women. Phenformin, a member of the biguanide class used to treat diabetes, has been identified for its capacity to enhance the suppression of cancer cell growth. This study's primary objective was to assess Phenformin's anticancer properties within hypoxic conditions in SKOV-3 human ovarian cancer cells. After exposing these cells to varying Phenformin concentrations (0.5 mM, 1 mM, 2 mM, 5 mM) for 24 hours, investigators conducted WST-1 cell viability and Annexin V apoptosis assays, uncovering a dose-dependent reduction in cell viability and an increase in apoptotic SKOV-3 cancer cells. Notably, Phenformin counteracted Cobalt(II) chloride-induced hypoxia-inducible factor-1alpha (HIF-1α) expression, with HIF-1α levels showing strong correlations with cell viability and apoptosis. Furthermore, Phenformin downregulated phosphoinositide-dependent kinase 1 (PDK1) expression in SKOV-3 ovarian cancer cells and effectively hindered their migratory capacity. This study underscores Phenformin's potential to induce apoptosis and impede proliferation in ovarian cancer cells under hypoxic conditions, with HIF-1α emerging as a promising therapeutic target for ovarian cancer treatment.
Gunaydin, Burcu. et al. "Cytotoxic effects of Phenformin on ovarian cancer cells: expression of HIF-1α and PDK1 in the hypoxic microenvironment." Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie, 2023.
Pubmed: 37867353   DOI: 10.47162/RJME.64.3.07

Jiang, Qiwei et al. "S6K1-mediated phosphorylation of PDK1 impairs AKT kinase activity and oncogenic functions." Nature communications vol. 13,1 1548. 22 Mar. 2022.
3-phosphoinositide-dependent protein kinase 1 (PDK1) serves as a central kinase, essential for phosphorylating and activating AGC family kinases, including AKT. However, understanding PDK1's upstream regulation has remained elusive. This study reveals that ribosomal protein S6 kinase beta 1 (S6K1), an AGC kinase downstream of mTORC1, directly phosphorylates PDK1 at its pleckstrin homology (PH) domain, disrupting PDK1's interaction with and activation of AKT. S6K1-mediated phosphorylation of PDK1 enhances its association with the 14-3-3 adaptor protein and homo-dimerization, detaching PDK1 from phosphatidylinositol 3,4,5 triphosphate (PIP3) and inhibiting its interaction with AKT. Mutations in patient-associated PDK1 further elevate AKT kinase activity and oncogenic potential. These findings unveil a nuanced feedback regulation of AKT signaling through S6K1-mediated PDK1 phosphorylation and suggest a potential strategy to combat mutant PDK1-driven cancers.
Jiang, Qiwei et al. "S6K1-mediated phosphorylation of PDK1 impairs AKT kinase activity and oncogenic functions." Nature communications vol. 13,1 1548. 22 Mar. 2022.
Pubmed: 35318320   DOI: 10.1038/s41467-022-28910-8