At least three mechanisms are thought to contribute to the metastasis-suppressive effect of Nm23-H1: (a) its histidine kinase activity toward ATP-citrate lyase, aldolase C, and the kinase suppressor of ras, with the last inactivating mitogen-activated protein kinase signaling; (b) binding proteins that titer out "free" Nm23-H1 and inhibit its ability to suppress metastasis; and (c) altered gene expression downstream of Nm23-H1, particularly an inverse association with the lysophosphatidic acid receptor endothelial differentiation gene-28 (EDG2).
Finally, to show the therapeutic potential and mechanism of ACLY inhibition for lung cancer treatment, we assessed the effect of RNA interference targeting ACLY on lipogenesis and cell proliferation in A549 cells.
Finally, to show the therapeutic potential and mechanism of ACLY inhibition for lung cancer treatment, we assessed the effect of RNA interference targeting ACLY on lipogenesis and cell proliferation in A549 cells.
Finally, to show the therapeutic potential and mechanism of ACLY inhibition for lung cancer treatment, we assessed the effect of RNA interference targeting ACLY on lipogenesis and cell proliferation in A549 cells.
To evaluate its role in lung cancer progression, we here analyzed ACLY expression in a subset of human lung adenocarcinoma cell lines and showed a relationship with the phosphatidyl-inositol-3 kinase-Akt pathway.
To better understand the biologic and molecular basis of distinction between cribriform HGPIN and IDC, we used break-apart fluorescence in-situ hybridization assay to assess ETS gene aberrations, a specific and commonest molecular alteration involving PCa, in a cohort of 16 isolated ACL, presumed to be an isolated cribriform HGPIN, and 45 carcinoma-associated ACL (ACL-PCa) on radical prostatectomy specimens, presumed to be spectrum of IDC-P.
A definitive role for ACL in tumorigenesis has emerged from ACL RNAi and chemical inhibitor studies, showing that ACL inhibition limits tumor cell proliferation and survival and induces differentiation in vitro.
Immunohistochemical analysis showed that phosphorylated ACL was increased in ovarian cancer tissues and that its expression correlated well with tumor grade, FIGO stage and poorer prognosis.
Taken together, our findings suggest that ACL may contribute to the pathogenesis of human epithelial ovarian cancer, and may serve as a novel therapeutic target.
Taken together, our findings suggest that ACL may contribute to the pathogenesis of human epithelial ovarian cancer, and may serve as a novel therapeutic target.
Metabolic pathways are built to elucidate the mechanisms by which VIRG host's higher energy requirements were met: including gene up-regulations for intestinal gluconeogenesis (PEPCK) and liver glycolysis (ENO2), and intriguingly liver fatty acid synthesis through ATP citrate synthase (CS) down-regulation and ATP citrate lyase (ACLY) and malic enzyme (ME) up-regulations.
We observed an increased expression of PDH and a decreased expression of ACL, PEPCK, and acetyl-GD3 in BD lymphoblast cells compared to normal cells, possibly resulting in the high ROS levels, mitochondrial membrane depolarization, and apoptosis typically found in BD.
NAFLD-specific expression and methylation differences were seen for nine genes coding for key enzymes in intermediate metabolism (including PC, ACLY, and PLCG1) and insulin/insulin-like signaling (including IGF1, IGFBP2, and PRKCE) and replicated by bisulfite pyrosequening (independent n = 39).
Future studies aim to utilize the detection of Aspergillus acl genes in PCR and microfluidic applications to determine the sensitivity and specificity for the identification of Aspergillus colonization and invasive aspergillosis in immunocompromised subjects.