-
Article
Open AccessThe therapeutic potential of RNA Polymerase I transcription inhibitor, CX-5461, in uterine leiomyosarcoma
Background. Uterine leiomyosarcoma is a rare aggressive smooth muscle cancer with poor survival rates. RNA Polymerase I (Pol I) activity is elevated in many cancers supporting tumour growth and prior studies in ...
-
Article
Open AccessThe RNA polymerase I transcription inhibitor CX-5461 cooperates with topoisomerase 1 inhibition by enhancing the DNA damage response in homologous recombination-proficient high-grade serous ovarian cancer
Intrinsic and acquired drug resistance represent fundamental barriers to the cure of high-grade serous ovarian carcinoma (HGSC), the most common histological subtype accounting for the majority of ovarian canc...
-
Article
Open AccessCX-5461 activates the DNA damage response and demonstrates therapeutic efficacy in high-grade serous ovarian cancer
Acquired resistance to PARP inhibitors (PARPi) is a major challenge for the clinical management of high grade serous ovarian cancer (HGSOC). Here, we demonstrate CX-5461, the first-in-class inhibitor of RNA po...
-
Article
Open AccessPGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth
Progesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells, where it is associated with detrimental patient outcomes. It contains phosphorylated tyrosines which evolutionarily preced...
-
Article
Open AccessA functional genetic screen defines the AKT-induced senescence signaling network
Exquisite regulation of PI3K/AKT/mTORC1 signaling is essential for homeostatic control of cell growth, proliferation, and survival. Aberrant activation of this signaling network is an early driver of many spor...
-
Article
Open AccessThe long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35
The majority of patients with neuroblastoma due to MYCN oncogene amplification and consequent N-Myc oncoprotein over-expression die of the disease. Here our analyses of RNA sequencing data identify the long nonco...
-
Article
Open AccessA novel small molecule that kills a subset of MLL-rearranged leukemia cells by inducing mitochondrial dysfunction
Survival rates for pediatric patients suffering from mixed lineage leukemia (MLL)-rearranged leukemia remain below 50% and more targeted, less toxic therapies are urgently needed. A screening method optimized to ...
-
Article
Open AccessChanges in long-range rDNA-genomic interactions associate with altered RNA polymerase II gene programs during malignant transformation
The three-dimensional organization of the genome contributes to its maintenance and regulation. While chromosomal regions associate with nucleolar ribosomal RNA genes (rDNA), the biological significance of rDN...
-
Article
Open AccessGenomic characterisation of Eμ-Myc mouse lymphomas identifies Bcor as a Myc co-operative tumour-suppressor gene
The Eμ-Myc mouse is an extensively used model of MYC driven malignancy; however to date there has only been partial characterization of MYC co-operative mutations leading to spontaneous lymphomagenesis. Here we s...
-
Article
Defective Hfp-dependent transcriptional repression of dMYC is fundamental to tissue overgrowth in Drosophila XPB models
Nucleotide excision DNA repair (NER) pathway mutations cause neurodegenerative and progeroid disorders (xeroderma pigmentosum (XP), Cockayne syndrome (CS) and trichothiodystrophy (TTD)), which are inexplicably...
-
Article
Open AccessPerturbations at the ribosomal genes loci are at the centre of cellular dysfunction and human disease
Ribosomal RNA (rRNA) gene (rDNA) transcription by RNA Polymerase I (Pol I) drives cell growth and underlies nucleolar structure and function, indirectly coordinating many fundamental cellular processes. The im...
-
Article
Dysregulation of the basal RNA polymerase transcription apparatus in cancer
The core RNA polymerase (Pol) subunits and general transcription factors (GTFs) are rarely mutated in cancer, although some GTFs are consistently overexpressed...
-
Article
The renin–angiotensin system and cancer: old dog, new tricks
This Review presents a contemporary update of the renin–angiotensin system (RAS), explaining its links to cancer through tissue remodelling, inflammation, angi...
-
Article
Chromatin organization and expression
A report on the 29th Lorne Genome Conference on the Organization and Expression of the Genome, Lorne, Australia, 17-21 February 2008.
-
Article
AngiotensinII mediates cardiomyocyte hypertrophic growth pathways via MMP-dependent HB-EGF liberation
Pathological cardiac stimulation by angiotensinII (AngII) can cause left ventricular hypertrophy, a major independent risk factor for heart attack and death. We have previously reported that AngII exerts its h...
-
Article
RNA polymerase I transcription in confluent cells: Rb downregulates rDNA transcription during confluence-induced cell cycle arrest
When 3T6 cells are confluent, they withdraw from the cell cycle. Concomitant with cell cycle arrest a significant reduction in RNA polymerase I transcription (80% decrease at 100% confluence) is observed. In t...
-
Chapter
Regulation of Ribosomal DNA Transcription During Cardiomyocyte Hypertrophy
Cardiomyocyte hypertrophy, induced by norepinephrine, endothelin-I, and contraction, is associated with increased rates of protein synthesis and reexpression of genes associated with the fetal gene program. Th...
