Identification of a GαGβγ, AKT and PKCα signalome associated with invasive growth in two genetic models of human breast cancer cell epithelial-to-mesenchymal transition.
In addition, we found using Bayesian network-based machine learning that 30 NRF1 motif-enriched genes including growth factor receptors-FGFR1, IGF1R; E2Fs transcription factor family-E2F1, E2F3; MAPK pathway-SHC2, GRB2, MAPK1; PI3K-AKT-mTOR signaling pathway-PIK3CD, PIK3R1, PIK3R3, RPS6KB2; WNT signaling pathway-WNT7B, DLV1, DLV2, GSK3B, NRF1, and DDB2, known for its role in DNA repair and involvement in early events associated with metastatic progression of breast cancer cells, were associated with HER2-amplified breast cancer.
Taken together, our results suggest that Notch-1-activating PI3K/AKT/NF-κB pathway is PP2A dependent; PP2A may be a potential therapeutic target in breast cancer.
The hotspot mutation H1047R in the oncogenic PIK3CA gene is frequently detected in breast cancer and enhances the enzymatic activity of PI3K to activate AKT/mTOR signaling cascade.
In this study, our stance was to investigate the regulatory mechanism of miR-190 on epithelial-mesenchymal transition (EMT) and angiogenesis via mediation of protein kinase B (AKT)-extracellular signal-regulated kinase (ERK) signaling pathway by targeting stanniocalicin 2 (STC2) in BC.
The assays are able to quantify AKT1 and AKT2 from breast cancer and colon cancer cell lines and flash-frozen tumor lysates with a linear range of 0.05-2.0 fmol/μg of total lysate protein and with coefficients of variation < 15%.
Recent study revealed that SGK3 plays a pivotal role in Akt/protein kinase B independent signaling downstream of oncogenic PI3KCA mutations in breast cancer.
Taken together, these results suggested that USP18 may serve a key role in breast cancer development by upregulating EGFR and subsequently activating the AKT/Skp2 feedback loop pathway.
We observed that loss of mitochondrial genome reversibly induced overexpression and activation of proto-oncogenic Ras, especially K-Ras 4A, responsible for the activation of AKT and ERK leading to advanced phenotype of prostate and breast cancer.
The common activation of the PI3K pathway in breast cancer has led to the development of compounds targeting the effector mechanisms of the pathway including selective and pan-PI3K/pan-AKT inhibitors, rapamycin analogs for mTOR inhibition, and TOR-catalytic subunit inhibitors.
The identification of palladin as an Akt1-specific substrate in our recently published work has exemplified distinct Akt isoform-specific signaling in breast cancer.