Journal: Signal Transduction and Targeted Therapy
Article Title: PKC-eta promotes breast cancer metastasis by regulating the Hippo–YAP signaling pathway
doi: 10.1038/s41392-026-02572-0
Figure Lengend Snippet: AKT phosphorylation of the upstream kinase cascade of the Hippo pathway is negatively regulated by PKCη. a Western blot analysis showing the activation of members of the upstream kinase cascade of the Hippo pathway, which is regulated by AKT phosphorylation, in PKCη KO TNBC cells. PKCη promotes YAP and PTEN expression, leading to dephosphorylation and inactivation of AKT. b An AKT inhibitor (MK-2206) effectively inhibits the upstream Hippo pathway phospho-cascade regulated by AKT in PKCη KO TNBC cells. c YAP-specific siRNA downregulates PTEN expression in TNBC cells in conjunction with AKT activation. d Relative mRNA expression of PTEN and PRKCH in control and MDA-MB-231 PKCη KO cells, as determined by RT‒qPCR. Knockout of PKCη in MDA-MB-231 cells resulted in a marked reduction in PTEN transcript levels compared with those in control cells. e Impact of PKCη expression on YAP transcriptional targets in TNBC cells. f Relative mRNA expression of canonical YAP target genes ( AXL, CYR61, IGFBP3 , and TEAD ) was measured via RT‒qPCR in MDA-MB-231 PKCη KO and control cells. PKCη knockout results in a significant reduction in the expression of these downstream effectors. g Schematic illustration of how YAP activity regulates PTEN expression and modulates the AKT pathway through this feedback mechanism (in the presence or absence of PKCη). Statistical significance was determined via two-way ANOVA, where * P < 0.05, ** P < 0.01, *** P < 0.001, and **** P < 0.0001
Article Snippet: The antibodies used in this study were against YAP (CST, #14074), MST1 (CST, #3682), pMST1 (CST, #3681), LATS1 (CST, #3477), 14-3-3 ζ/δ (CST, #7413), pLATS1 (CST, #8654), pYAP (Ser127) (CST, #13008), pYAP (Ser109) (CST, #53749), pYAP (Ser397) (CST, #13619), pTAZ (Ser89) (CST, #75275), TAZ (CST, #83669), PTEN (CST, #9559) Lamin B1 (CST, #13435), AKT (pan) (CST, #4691), AXL (CST, #8661), Pan-TEAD (CST, #13295), CYR61 (CST, 14479), IGFBP3 (CST, #25864), HA-Tag (CST, #3724), FLAG (CST, #14793), pAKT (Ser473) (CST, #4060), and Anti-rabbit IgG (CST, # 7074).
Techniques: Phospho-proteomics, Western Blot, Activation Assay, Expressing, De-Phosphorylation Assay, Control, Knock-Out, Activity Assay