Pathway enrichment analysis suggested that adhesion kinase, ECM-receptor interaction, calcium signaling, Wnt pathways, and PI3K/AKT signaling pathway are highly associated with breast cancer bone metastasis.
Recently, results from our laboratory have shown that MICAL1 modulates reactive oxygen species (ROS) production, and the latter then activates phosphatidyl inositol 3-kinase (PI3K)/protein kinase B (Akt) signalling pathway which regulates breast cancer cell invasion.
Collectively, the results above demonstrated that miR-425-5p was involved in the tumorigenesis of breast cancer by inducing PI3K/AKT signaling and indicated that miR-425-5p could be as a potential target for breast cancer therapy in the future.
Altogether, our results revealed that miR-326 play a tumor-suppressive role in breast cancer through inhibiting ErbB/PI3K pathway and miR-326 may serve as a potential therapeutic target for the treatment of patients with breast cancer.
Endocrine resistance in breast cancer remains a major clinical problem and is caused by crosstalk mechanisms of growth factor receptor cascades, such as the erbB and PI3K/AKT pathways.
Using comprehensive multi-omic molecular profiling, we assessed whether alterations or activation of the PI3K-AKT-mTOR pathway is associated with specific sites of breast cancer metastasis.<b>Experimental Design:</b> Next-generation sequencing-based whole-exome sequencing was coupled with reverse-phase protein microarray (RPPA) functional signaling network analysis to explore the PI3K-AKT-mTOR axis in 32 pretreated breast cancer metastases.
Two inhibitors of phosphatidylinositol 3-kinase (PI3K) pathway taselisib, targeting the mutant PI3K-subunit-alpha (PI3KA) and ipatasertib, AKT-inhibitor, are currently under clinical investigation in breast cancer (BC) patients.
Mutations in the oncogene, PIK3CA, are frequently observed in breast cancer and have been suggested as a predictive biomarker for PI3K-selective inhibitor treatment.
Results from the in vivo and in vitro experiments both showed that fucoidan decreased the levels of p-PI3K, p-AKT and p-GSK-3β (Ser9) in breast cancer.
Using a panel of small-molecule PI3K isoform-selective inhibitors in a diverse set of breast cancer cell lines, we have demonstrated that the biochemical and biological responses were highly variable and dependent on the genetic alterations present. p110alpha inhibitors were generally effective in inhibiting the phosphorylation of PKB (protein kinase B)/Akt and S6, two downstream components of PI3K signalling, in most cell lines examined.
<b>Conclusion:</b> We provide the first evidence of the involvement of IRF6 in breast cancer pathogenesis, which was found to modulate the PI3K/AKT pathway via mediating PIK3R2; indicating that IRF6 can be targeted as a potential therapeutic treatment of breast cancer.
This cell line and its orthotopic xenograft models were exposed to p110α-specific inhibitor BYL719, p110β-specific inhibitor AZD6482, or pan-PI3K inhibitor BKM120, respectively, and the results showed sensitivity to both BYL719 and BKM120 but not AZD6482, which indicated a p110α-reliance for HER2-positive-PTEN-loss breast cancer.
Overall, our findings suggest SIK2 as a potential tumor suppressor in the control of breast tumorigenesis, at least in part, <i>via</i> inhibiting PI3K/Akt and Ras/ERK signaling cascades simultaneously and a novel prognostic marker, especially in basal subtypes of breast cancer.
The phosphoinositide-3-kinase (PI3K) pathway is commonly deregulated in breast cancer through several mechanisms, including PIK3CA mutation and loss of phosphatase and tensin homolog (PTEN) and inositol polyphosphate 4-phosphatase-II (INPP4B).
Particularly, miR-130b mediated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway as well as the chemoresistance and proliferation of breast cancer cell lines, which was partially blocked following knockdown of PTEN.
To this end, we have determined the growth response to inhibition of the PI3K/Akt signaling pathway in a series of breast cancer cell lines with different PTEN levels.