Open Access. Powered by Scholars. Published by Universities.®
- Keyword
-
- Humans (3)
- Mitochondria (3)
- Animals (2)
- Cell Line (2)
- Cytokines (2)
-
- Inbred C57BL (2)
- Mice (2)
- Signal Transduction (2)
- Tumor (2)
- A549 Cells (1)
- Actin (1)
- Adult (1)
- Apoptosis (1)
- Bacterial (1)
- Bacteroides (1)
- CD4-Positive T-Lymphocytes (1)
- CD8-Positive T-Lymphocytes (1)
- Cancer metabolism (1)
- Carcinoma (1)
- Clostridiales (1)
- DNA (1)
- DNA Methylation (1)
- Diabetes Mellitus (1)
- Enzyme Inhibitors (1)
- Epigenesis (1)
- Farnesyltranstransferase (1)
- Fascin (1)
- Female (1)
- Gastrointestinal Microbiome (1)
- Gemcitabine (1)
Articles 1 - 7 of 7
Full-Text Articles in Oncology
The Mitochondrial Deoxyguanosine Kinase Is Required For Cancer Cell Stemness In Lung Adenocarcinoma, Shengchen Lin, Chongbiao Huang, Jianwei Sun, Oana Bollt, Xiuchao Wang, Eric Martine, Jiaxin Kang, Matthew D. Taylor, Bin Fang, Pankaj K. Singh, John Koomen, Jihui Hao, Shengyu Yang
The Mitochondrial Deoxyguanosine Kinase Is Required For Cancer Cell Stemness In Lung Adenocarcinoma, Shengchen Lin, Chongbiao Huang, Jianwei Sun, Oana Bollt, Xiuchao Wang, Eric Martine, Jiaxin Kang, Matthew D. Taylor, Bin Fang, Pankaj K. Singh, John Koomen, Jihui Hao, Shengyu Yang
Journal Articles: Eppley Institute
The mitochondrial deoxynucleotide triphosphate (dNTP) is maintained by the mitochondrial deoxynucleoside salvage pathway and dedicated for the mtDNA homeostasis, and the mitochondrial deoxyguanosine kinase (DGUOK) is a rate-limiting enzyme in this pathway. Here, we investigated the role of the DGUOK in the self-renewal of lung cancer stem-like cells (CSC). Our data support that DGUOK overexpression strongly correlates with cancer progression and patient survival. The depletion of DGUOK robustly inhibited lung adenocarcinoma tumor growth, metastasis, and CSC self-renewal. Mechanistically, DGUOK is required for the biogenesis of respiratory complex I and mitochondrial OXPHOS, which in turn regulates CSC self-renewal through AMPK-YAP1 signaling. …
Mitochondrial Superoxide Disrupts The Metabolic And Epigenetic Landscape Of Cd4, Cassandra M. Moshfegh, Christopher W. Collins, Venugopal Gunda, A. Vasanthakumar, J. Z. Cao, Pankaj K. Singh, L. A. Godley, Adam J. Case
Mitochondrial Superoxide Disrupts The Metabolic And Epigenetic Landscape Of Cd4, Cassandra M. Moshfegh, Christopher W. Collins, Venugopal Gunda, A. Vasanthakumar, J. Z. Cao, Pankaj K. Singh, L. A. Godley, Adam J. Case
Journal Articles: Eppley Institute
While the role of mitochondrial metabolism in controlling T-lymphocyte activation and function is becoming more clear, the specifics of how mitochondrial redox signaling contributes to T-lymphocyte regulation remains elusive. Here, we examined the global effects of elevated mitochondrial superoxide (O2-) on T-lymphocyte activation using a novel model of inducible manganese superoxide dismutase (MnSOD) knock-out. Loss of MnSOD led to specific increases in mitochondrial O2- with no evident changes in hydrogen peroxide (H2O2), peroxynitrite (ONOO-), or copper/zinc superoxide dismutase (CuZnSOD) levels. Unexpectedly, both mitochondrial and glycolytic metabolism showed significant reductions …
Selective Inhibition Of Histone Deacetylases 1/2/6 In Combination With Gemcitabine: A Promising Combination For Pancreatic Cancer Therapy, Richard S. Laschanzky, Lisa E. Humphrey, Jihyun Ma, Lynette M. Smith, Thomas J. Enke, Surendra K. Shukla, Aneesha Dasgupta, Pankaj K. Singh, Gillian M. Howell, Michael G. Brattain, Quan P. Ly, Adrian R. Black, Jennifer D. Black
Selective Inhibition Of Histone Deacetylases 1/2/6 In Combination With Gemcitabine: A Promising Combination For Pancreatic Cancer Therapy, Richard S. Laschanzky, Lisa E. Humphrey, Jihyun Ma, Lynette M. Smith, Thomas J. Enke, Surendra K. Shukla, Aneesha Dasgupta, Pankaj K. Singh, Gillian M. Howell, Michael G. Brattain, Quan P. Ly, Adrian R. Black, Jennifer D. Black
Journal Articles: Eppley Institute
Pancreatic ductal adenocarcinoma (PDAC) has a five-year survival rate of <10% due in part to a lack of effective therapies. Pan-histone deacetylase (HDAC) inhibitors have shown preclinical efficacy against PDAC but have failed in the clinic due to toxicity. Selective HDAC inhibitors may reduce toxicity while retaining therapeutic efficacy. However, their use requires identification of the specific HDACs that mediate the therapeutic effects of HDAC inhibitors in PDAC. We determined that the HDAC1/2/3 inhibitor Mocetinostat synergizes with the HDAC4/5/6 inhibitor LMK-235 in a panel of PDAC cell lines. Furthermore, while neither drug alone synergizes with gemcitabine, the combination of Mocetinostat, LMK-235, and gemcitabine showed strong synergy. Using small interfering (si)RNA-mediated knockdown, this synergy was attributed to inhibition of HDACs 1, 2, and 6. Pharmacological inhibition of HDACs 1 and 2 with Romidepsin and HDAC6 with ACY-1215 also potently synergized with gemcitabine in a panel of PDAC cell lines, and this drug combination potentiated the antitumor effects of gemcitabine against PDAC xenografts in vivo. Collectively, our data show that inhibition of multiple HDACs is required for therapeutic effects of HDAC inhibitors and support the development of novel strategies to inhibit HDACs 1, 2, and 6 for PDAC therapy.
Fascin Controls Metastatic Colonization And Mitochondrial Oxidative Phosphorylation By Remodeling Mitochondrial Actin Filaments, Shengchen Lin, Chongbiao Huang, Venugopal Gunda, Jianwei Sun, Srikumar P. Chellappan, Zengxun Li, Victoria Izumi, Bin Fang, John Koomen, Pankaj K. Singh, Jihui Hao, Shengyu Yang
Fascin Controls Metastatic Colonization And Mitochondrial Oxidative Phosphorylation By Remodeling Mitochondrial Actin Filaments, Shengchen Lin, Chongbiao Huang, Venugopal Gunda, Jianwei Sun, Srikumar P. Chellappan, Zengxun Li, Victoria Izumi, Bin Fang, John Koomen, Pankaj K. Singh, Jihui Hao, Shengyu Yang
Journal Articles: Eppley Institute
The deregulation of the actin cytoskeleton has been extensively studied in metastatic dissemination. However, the post-dissemination role of the actin cytoskeleton dysregulation is poorly understood. Here, we report that fascin, an actin-bundling protein, promotes lung cancer metastatic colonization by augmenting metabolic stress resistance and mitochondrial oxidative phosphorylation (OXPHOS). Fascin is directly recruited to mitochondria under metabolic stress to stabilize mitochondrial actin filaments (mtF-actin). Using unbiased metabolomics and proteomics approaches, we discovered that fascin-mediated mtF-actin remodeling promotes mitochondrial OXPHOS by increasing the biogenesis of respiratory Complex I. Mechanistically, fascin and mtF-actin control the homeostasis of mtDNA to promote mitochondrial OXPHOS. The …
Human Islet Response To Selected Type 1 Diabetes-Associated Bacteria: A Transcriptome-Based Study, Ahmed M. Abdellatif, Heather Jensen Smith, Robert Z. Harms, Nora Sarvetnick
Human Islet Response To Selected Type 1 Diabetes-Associated Bacteria: A Transcriptome-Based Study, Ahmed M. Abdellatif, Heather Jensen Smith, Robert Z. Harms, Nora Sarvetnick
Journal Articles: Eppley Institute
Type 1 diabetes (T1D) is a chronic autoimmune disease that results from destruction of pancreatic β-cells. T1D subjects were recently shown to harbor distinct intestinal microbiome profiles. Based on these findings, the role of gut bacteria in T1D is being intensively investigated. The mechanism connecting intestinal microbial homeostasis with the development of T1D is unknown. Specific gut bacteria such as Bacteroides dorei (BD) and Ruminococcus gnavus (RG) show markedly increased abundance prior to the development of autoimmunity. One hypothesis is that these bacteria might traverse the damaged gut barrier, and their constituents elicit a response from human islets that causes …
Metabolic Alterations In Pancreatic Cancer Progression, Enza Vernucci, Jaime Abrego, Venugopal Gunda, Surendra K. Shukla, Aneesha Dasgupta, Vikrant Rai, Nina V. Chaika, Kyla Buettner, Alysha Illies, Fang Yu, Audrey J. Lazenby, Benjamin J. Swanson, Pankaj K. Singh
Metabolic Alterations In Pancreatic Cancer Progression, Enza Vernucci, Jaime Abrego, Venugopal Gunda, Surendra K. Shukla, Aneesha Dasgupta, Vikrant Rai, Nina V. Chaika, Kyla Buettner, Alysha Illies, Fang Yu, Audrey J. Lazenby, Benjamin J. Swanson, Pankaj K. Singh
Journal Articles: Eppley Institute
Pancreatic cancer is the third leading cause of cancer-related deaths in the USA. Pancreatic tumors are characterized by enhanced glycolytic metabolism promoted by a hypoxic tumor microenvironment and a resultant acidic milieu. The metabolic reprogramming allows cancer cells to survive hostile microenvironments. Through the analysis of the principal metabolic pathways, we identified the specific metabolites that are altered during pancreatic cancer progression in the spontaneous progression (KPC) mouse model. Genetically engineered mice exhibited metabolic alterations during PanINs formation, even before the tumor development. To account for other cells in the tumor microenvironment and to focus on metabolic adaptations concerning tumorigenic …
Inhibition Of Geranylgeranyl Diphosphate Synthase Is A Novel Therapeutic Strategy For Pancreatic Ductal Adenocarcinoma, Staci L. Haney, Michelle L. Varney, Yashpal S. Chhonker, Simon Shin, Kamiya Mehla, Ayrianne J. Crawford, Heather Jensen Smith, Lynette M. Smith, Daryl J. Murry, Michael A. Hollingsworth, Sarah A. Holstein
Inhibition Of Geranylgeranyl Diphosphate Synthase Is A Novel Therapeutic Strategy For Pancreatic Ductal Adenocarcinoma, Staci L. Haney, Michelle L. Varney, Yashpal S. Chhonker, Simon Shin, Kamiya Mehla, Ayrianne J. Crawford, Heather Jensen Smith, Lynette M. Smith, Daryl J. Murry, Michael A. Hollingsworth, Sarah A. Holstein
Journal Articles: Eppley Institute
Rab proteins play an essential role in regulating intracellular membrane trafficking processes. Rab activity is dependent upon geranylgeranylation, a post-translational modification that involves the addition of 20-carbon isoprenoid chains via the enzyme geranylgeranyl transferase (GGTase) II. We have focused on the development of inhibitors against geranylgeranyl diphosphate synthase (GGDPS), which generates the isoprenoid donor (GGPP), as anti-Rab agents. Pancreatic ductal adenocarcinoma (PDAC) is characterized by abnormal mucin production and these mucins play important roles in tumor development, metastasis and chemo-resistance. We hypothesized that GGDPS inhibitor (GGDPSi) treatment would induce PDAC cell death by disrupting mucin trafficking, thereby inducing the unfolded …