A5045298703- Histone Deacetylase Inhibitors Research
- PARP inhibition in cancer therapy
- Cancer Cells and Metastasis
- Cancer Mechanisms and Therapy
- Advanced Breast Cancer Therapies
- Epigenetics and DNA Methylation
- FOXO transcription factor regulation
- Protein Degradation and Inhibitors
- Melanoma and MAPK Pathways
- Genetic factors in colorectal cancer
- Cancer, Lipids, and Metabolism
- RNA modifications and cancer
- Cancer, Stress, Anesthesia, and Immune Response
- Cancer Treatment and Pharmacology
- Autophagy in Disease and Therapy
- Apelin-related biomedical research
- Cancer-related gene regulation
- Ferroptosis and cancer prognosis
- Lipid metabolism and disorders
- Colorectal Cancer Treatments and Studies
- Kruppel-like factors research
- Digestive system and related health
- Ubiquitin and proteasome pathways
- Biomedical Research and Pathophysiology
- Helicobacter pylori-related gastroenterology studies
Olivia Newton-John Cancer Wellness & Research Centre
2016-2025
La Trobe University
2016-2025
Ludwig Cancer Research
2016-2017
Inhibitors of the bromodomain and extraterminal domain (BET) protein family attenuate proliferation several tumor cell lines. These effects are mediated, at least in part, through repression c-MYC. In colorectal cancer, overexpression c-MYC due to hyperactive WNT/β-catenin/TCF signaling is a key driver progression; however, effective strategies target this oncogene remain elusive. Here, we investigated effect BET inhibitors (BETi) on cancer expression. Treatment 20 lines with BETi JQ1...
Abstract Histone deacetylase 3 ( Hdac3 ) regulates the expression of lipid metabolism genes in multiple tissues, however its role regulating intestinal epithelium is unknown. Here we demonstrate that intestine-specific deletion IKO protects mice from diet induced obesity. Intestinal epithelial cells (IECs) display co-ordinate induction and proteins involved mitochondrial peroxisomal β-oxidation, have an increased rate fatty acid oxidation, undergo marked remodelling their lipidome,...
Abstract Purpose: Histone deacetylase inhibitors (HDACi) are epigenome-targeting small molecules approved for the treatment of cutaneous T-cell lymphoma and multiple myeloma. They have also demonstrated clinical activity in acute myelogenous leukemia, non–small cell lung cancer, estrogen receptor–positive breast trials underway assessing their combination regimens including immunotherapy. However, there is currently no clear strategy to reliably predict HDACi sensitivity. In colon cancer...
Autophagy-related genes have been closely associated with intestinal homeostasis. BECLIN1 is a component of Class III phosphatidylinositol 3-kinase complexes that orchestrate autophagy initiation and endocytic trafficking. Here we show epithelium-specific deletion in adult mice leads to rapid fatal enteritis compromised gut barrier integrity, highlighting its intrinsic critical role maintenance. BECLIN1-deficient epithelial cells exhibit extensive apoptosis, impaired autophagy, stressed...
Abstract The EGFR/RAS/MEK/ERK signaling pathway (ERK/MAPK) is hyperactivated in most colorectal cancers. A current limitation of inhibitors this that they primarily induce cytostatic effects cancer cells. Nevertheless, these drugs do expression proapoptotic factors, suggesting may prime cells to undergo apoptosis. As histone deacetylase (HDACis) multiple proteins, we examined whether could synergize with ERK/MAPK trigger cell Combined MEK/ERK and HDAC inhibition synergistically induced...
Colorectal cancers (CRCs) often display histological features indicative of aberrant differentiation but the molecular underpinnings this trait and whether it directly drives disease progression is unclear. Here, we identify co-ordinate epigenetic inactivation two epithelial-specific transcription factors, EHF CDX1, as a mechanism driving loss in CRCs. Re-expression CDX1 poorly-differentiated CRC cells induced extensive chromatin remodelling, transcriptional re-programming, along enterocytic...
ABSTRACT Ets homologous factor (EHF) is a member of the epithelial-specific (ESE) family transcription factors. To investigate its role in development and epithelial homeostasis, we generated series novel mouse strains which DNA-binding domain Ehf was deleted all tissues (Ehf−/−) or specifically gut epithelium. Ehf−/− mice were born at expected Mendelian ratio, but showed reduced body weight gain, developed pathologies requiring most to reach an ethical endpoint before reaching 1 year age....
The ERK signalling pathway regulates key cell fate decisions in the intestinal epithelium and is frequently dysregulated colorectal cancers (CRCs). Variations dynamics of activation can induce different biological outcomes are regulated by multiple mechanisms, including negative feedback loops involving transcriptional induction dual-specificity phosphatases (DUSPs). We have found that nuclear ERK-selective phosphatase DUSP5 downregulated tumours lines, as previously observed gastric...
High-fat (HF) diets (HFDs) and inflammation are risk factors for colon cancer; however, the underlying mechanisms remain to be fully elucidated. The transcriptional corepressor HDAC3 has recently emerged as a key regulator of intestinal epithelial responses diet with intestinal-specific Hdac3 deletion (Hdac3IKO) in mice increasing fatty acid oxidation genes rate enterocytes. Hdac3IKO also predisposed experimentally induced colitis; whether this is driven by metabolic reprogramming...
Abstract Histone deacetylase inhibitors (HDACi) are approved for the treatment of cutaneous T-Cell lymphoma (CTCL) and Multiple Myeloma. In colon cancer cells HDACi-induced apoptosis is linked to induction a specific transcriptional response involving upregulation immediate-early (IE) genes FOS, JUN, EGR1, EGR3 ATF3. To determine if this underpins across multiple tumour types, including CTCL MM, 50 cell lines derived from common solid haematological cancers were screened sensitivity...
<p>Supplementary figure 2 shows the effect of trametinib plus panobinostat on colony formation in HCT 116 cells</p>
<p>Supplementary figure 3 shows combining trametinib with different classes of HDAC inhibitors in COLO 201 cells</p>
<div>Abstract<p>The EGFR/RAS/MEK/ERK signaling pathway (ERK/MAPK) is hyperactivated in most colorectal cancers. A current limitation of inhibitors this that they primarily induce cytostatic effects cancer cells. Nevertheless, these drugs do expression proapoptotic factors, suggesting may prime cells to undergo apoptosis. As histone deacetylase (HDACis) multiple proteins, we examined whether could synergize with ERK/MAPK trigger cell Combined MEK/ERK and HDAC inhibition...
<p>Supplementary Figure 1 shows the synergistic effect of trametinib plus panobinostat in CRC cell lines and PDTO's</p>
<p>Supplementary figure 2 shows the effect of trametinib plus panobinostat on colony formation in HCT 116 cells</p>
<p>Supplementary figure 3 shows combining trametinib with different classes of HDAC inhibitors in COLO 201 cells</p>
<div>Abstract<p>The EGFR/RAS/MEK/ERK signaling pathway (ERK/MAPK) is hyperactivated in most colorectal cancers. A current limitation of inhibitors this that they primarily induce cytostatic effects cancer cells. Nevertheless, these drugs do expression proapoptotic factors, suggesting may prime cells to undergo apoptosis. As histone deacetylase (HDACis) multiple proteins, we examined whether could synergize with ERK/MAPK trigger cell Combined MEK/ERK and HDAC inhibition...
<p>Supplementary figure 4 shows phosphorylated ERK staining in an adenoma from a ACDX2 mouse</p>
<p>Supplementary figure 5 shows mouse weight during treatment in two of the studies</p>
<p>Supplementary Figure 1 shows the synergistic effect of trametinib plus panobinostat in CRC cell lines and PDTO's</p>