In addition, genetic deletion of 4E-BP1 and 4E-BP2 significantly accelerates all phases of cancer development in the context of PTEN loss-driven prostate cancer in mice despite potent PI3K/AKT and mTOR activation.
However, signaling pathways driving aberrant IAS remain poorly understood.<b>Experimental Design:</b> The effect of components of the AKT-RUNX2-osteocalcin (OCN)-GPRC6A-CREB signaling axis on expression of steroidogenesis genes <i>CYP11A1</i> and <i>CYP17A1</i> and testosterone level were examined in PTEN-null human prostate cancer cell lines.
Knockdown of Phospholipase Cε (PLCε) Inhibits Cell Proliferation via Phosphatase and Tensin Homolog Deleted on Chromosome 10 (PTEN)/AKT Signaling Pathway in Human Prostate Cancer.
Multifractionated radiation of three-dimensional-cultured prostate cancer cell lines with a dose of 2 Gy/day as a clinically relevant schedule resulted in an increased protein phosphorylation and enhanced protein-protein interaction between AKT and mTOR, whereas gene expression of <i>AKT, MTOR</i>, and related kinases was not altered by radiation.
Our study identifies HDAC3 as a common upstream activator of AKT and AR signaling and reveals that dual inhibition of AKT and AR pathways is achievable by single-agent targeting of HDAC3 in prostate cancer.
In addition, LY294002, an protein kinase B (Akt) inhibitor, greatly suppressed the expression level of phospho (p)‑Akt, matrix metalloproteinase (MMP)‑9 and p‑mammalian target of rapamycin (mTOR), suggesting that the activation of the Akt/mTOR/MMP‑9 signaling pathway may participate in regulating cell migration in PCa.
Developing combination therapy for castrate-resistant prostate cancer (CRPC) may require exploiting new drug targets outside androgen receptor and PI3K / AKT / mTOR signal transduction pathways implicated in prostate cancer (PCa) progression.
The overexpression of trefoil factor family 3 (TFF3) is observed in a variety of cancers, including prostate cancer (PCa), and its potential role in carcinogenesis, such as activating the PI3K/AKT pathway, is suggested.
By conducting transcriptome analysis, denaturing immunoprecipitations and immunopathology, we demonstrate that the TP53-MDM2-AR-AKT cross-talk is regulated by the deubiquitinating enzyme USP12 in prostate cancer.
The bioinformatics of prostate cancer and CHRM pathways show that the downstream signalling include PIP3-AKT-CaM-mediated growth in LNCaP and PC3 cells.
These data argue for AKT-associated HK2-mediated metabolic reprogramming and mitochondrial association in PI3K-driven prostate cancer as one survival mechanism downstream of AR inhibition.
The observed reduction in soft tissue tumor burden corresponded to a biochemical reduction in Rap1A geranylgeranylation, which for prostate cancer is important in its own merit and which serves as a surrogate marker for Rho family, i.e.Rac, protein modification.
Notably, RGS12 exhibited potent tumor-suppressor activity in prostate cancer and prostate epithelial cell lines <i>in vitro</i> and <i>in vivo</i> We found that RGS12 expression correlated negatively with the oncogene MNX1 and regulated its expression <i>in vitro</i> and <i>in vivo</i> Further, MNX1 was regulated by AKT activity, and RGS12 expression decreased total and activated AKT levels.
Our study found that the variant genotype CT of rs3730358 of AKT1 was associated with a decreased risk of prostate cancer, which suggested that this polymorphism could play an important role in the development of the disease.