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Pancreatic Neoplasms: HELP
Articles by Roger J. Daly
Based on 5 articles published since 2009
(Why 5 articles?)
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Between 2009 and 2019, Roger J. Daly wrote the following 5 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Resolution of Novel Pancreatic Ductal Adenocarcinoma Subtypes by Global Phosphotyrosine Profiling. 2016

Humphrey, Emily S / Su, Shih-Ping / Nagrial, Adnan M / Hochgräfe, Falko / Pajic, Marina / Lehrbach, Gillian M / Parton, Robert G / Yap, Alpha S / Horvath, Lisa G / Chang, David K / Biankin, Andrew V / Wu, Jianmin / Daly, Roger J. ·From the ‡Cancer Division and Kinghorn Cancer Centre, Garvan Institute of Medical Research, 384 Victoria St, Sydney, NSW 2010, Australia; §St Vincent's Hospital Clinical School, Faculty of Medicine, University of New South Wales, NSW 2052, Australia; · ¶Cancer Program, Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Level 1, Building 77, Monash University, VIC 3800, Australia; · ‖Competence Center Functional Genomics, University of Greifswald, F.-L-Jahnstr. 15, 17489 Greifswald, Germany; · From the ‡Cancer Division and Kinghorn Cancer Centre, Garvan Institute of Medical Research, 384 Victoria St, Sydney, NSW 2010, Australia; · **Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane QLD 4072, Australia; · From the ‡Cancer Division and Kinghorn Cancer Centre, Garvan Institute of Medical Research, 384 Victoria St, Sydney, NSW 2010, Australia; ‡‡Chris O'Brien Lifehouse, Missenden Road, Camperdown, NSW 2050, Australia; · §§Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK; · §§Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK; andrew.biankin@glasgow.ac.uk. · ¶¶Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center for Cancer Bioinformatics, Peking University Cancer Hospital & Institute, 52 Fu-Cheng Road, Hai-Dian District, Beijing 100142, China From the ‡Cancer Division and Kinghorn Cancer Centre, Garvan Institute of Medical Research, 384 Victoria St, Sydney, NSW 2010, Australia; §St Vincent's Hospital Clinical School, Faculty of Medicine, University of New South Wales, NSW 2052, Australia; roger.daly@monash.edu wujm@bjmu.edu.cn. · ¶Cancer Program, Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Level 1, Building 77, Monash University, VIC 3800, Australia; roger.daly@monash.edu wujm@bjmu.edu.cn. ·Mol Cell Proteomics · Pubmed #27259358.

ABSTRACT: Comprehensive characterization of signaling in pancreatic ductal adenocarcinoma (PDAC) promises to enhance our understanding of the molecular aberrations driving this devastating disease, and may identify novel therapeutic targets as well as biomarkers that enable stratification of patients for optimal therapy. Here, we use immunoaffinity-coupled high-resolution mass spectrometry to characterize global tyrosine phosphorylation patterns across two large panels of human PDAC cell lines: the ATCC series (19 cell lines) and TKCC series (17 cell lines). This resulted in the identification and quantification of over 1800 class 1 tyrosine phosphorylation sites and the consistent segregation of both PDAC cell line series into three subtypes with distinct tyrosine phosphorylation profiles. Subtype-selective signaling networks were characterized by identification of subtype-enriched phosphosites together with pathway and network analyses. This revealed that the three subtypes characteristic of the ATCC series were associated with perturbations in signaling networks associated with cell-cell adhesion and epithelial-mesenchyme transition, mRNA metabolism, and receptor tyrosine kinase (RTK) signaling, respectively. Specifically, the third subtype exhibited enhanced tyrosine phosphorylation of multiple RTKs including the EGFR, ERBB3 and MET. Interestingly, a similar RTK-enriched subtype was identified in the TKCC series, and 'classifier' sites for each series identified using Random Forest models were able to predict the subtypes of the alternate series with high accuracy, highlighting the conservation of the three subtypes across the two series. Finally, RTK-enriched cell lines from both series exhibited enhanced sensitivity to the small molecule EGFR inhibitor erlotinib, indicating that their phosphosignature may provide a predictive biomarker for response to this targeted therapy. These studies highlight how resolution of subtype-selective signaling networks can provide a novel taxonomy for particular cancers, and provide insights into PDAC biology that can be exploited for improved patient management.

2 Article The pseudokinase SgK223 promotes invasion of pancreatic ductal epithelial cells through JAK1/Stat3 signaling. 2015

Tactacan, Carole M / Phua, Yu Wei / Liu, Ling / Zhang, Luxi / Humphrey, Emily S / Cowley, Mark / Pinese, Mark / Biankin, Andrew V / Daly, Roger J. ·Cancer Research Division, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, NSW, 2010, Australia. carole.tactacan@gmail.com. · Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, 3800, Australia. carole.tactacan@gmail.com. · Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, 3800, Australia. yuwei.phua@monash.edu. · Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, 3800, Australia. ling.liu@monash.edu. · Cancer Research Division, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, NSW, 2010, Australia. luxi.zhang@monash.edu. · Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, 3800, Australia. luxi.zhang@monash.edu. · Cancer Research Division, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, NSW, 2010, Australia. ehumphrey@biochem.mpg.de. · Cancer Research Division, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, NSW, 2010, Australia. m.cowley@garvan.org.au. · Cancer Research Division, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, NSW, 2010, Australia. m.pinese@garvan.org.au. · Cancer Research Division, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, NSW, 2010, Australia. andrew.biankin@glasgow.ac.uk. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Scotland, G61 1BD, UK. andrew.biankin@glasgow.ac.uk. · Cancer Research Division, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, NSW, 2010, Australia. roger.daly@monash.edu. · Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, 3800, Australia. roger.daly@monash.edu. · Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Level 1, Building 77, 23 Innovation Walk, Monash, VIC, 3800, Australia. roger.daly@monash.edu. ·Mol Cancer · Pubmed #26215634.

ABSTRACT: BACKGROUND: Characterization of molecular mechanisms underpinning development of pancreatic ductal adenocarcinoma (PDAC) may lead to the identification of novel therapeutic targets and biomarkers. SgK223, also known as Pragmin, is a pseudokinase and scaffolding protein closely related to SgK269/PEAK1. Both proteins are implicated in oncogenic tyrosine kinase signaling, but their mechanisms and function remain poorly characterized. METHODS: Expression of SgK223 in PDAC and PDAC cell lines was characterized using gene expression microarrays, mass spectrometry (MS)-based phosphoproteomics and Western blotting. SgK223 was overexpressed in human pancreatic ductal epithelial (HPDE) cells via retroviral transduction, and knocked down in PDAC cells using siRNA. Cell proliferation was determined using a colorimetric cell viability assay, and cell migration and invasion using transwells. Expression of markers of epithelial-mesenchyme transition (EMT) was assayed by quantitative PCR. SgK223 and Stat3 signaling was interrogated by immunoprecipitation, Western blot and gene reporter assays. The functional role of specific kinases and Stat3 was determined using selective small molecule inhibitors. RESULTS: Elevated site-selective tyrosine phosphorylation of SgK223 was identified in subsets of PDAC cell lines, and increased expression of SgK223 detected in several PDAC cell lines compared to human pancreatic ductal epithelial (HPDE) cells and in PDACs compared to normal pancreas. Expression of SgK223 in HPDE cells at levels comparable to those in PDAC did not alter cell proliferation but led to a more elongated morphology, enhanced migration and invasion and induced gene expression changes characteristic of a partial EMT. While SgK223 overexpression did not affect activation of Erk or Akt, it led to increased Stat3 Tyr705 phosphorylation and Stat3 transcriptional activity, and SgK223 and Stat3 associated in vivo. SgK223-overexpressing cells exhibited increased JAK1 activation, and use of selective inhibitors determined that the increased Stat3 signaling driven by SgK223 was JAK-dependent. Pharmacological inhibition of Stat3 revealed that Stat3 activation was required for the enhanced motility and invasion of SgK223-overexpressing cells. CONCLUSIONS: Increased expression of SgK223 occurs in PDAC, and overexpression of SgK223 in pancreatic ductal epithelial cells promotes acquisition of a migratory and invasive phenotype through enhanced JAK1/Stat3 signaling. This represents the first association of SgK223 with a particular human cancer, and links SgK223 with a major signaling pathway strongly implicated in PDAC progression.

3 Article Neuropilin-2 promotes extravasation and metastasis by interacting with endothelial α5 integrin. 2013

Cao, Ying / Hoeppner, Luke H / Bach, Steven / E, Guangqi / Guo, Yan / Wang, Enfeng / Wu, Jianmin / Cowley, Mark J / Chang, David K / Waddell, Nicola / Grimmond, Sean M / Biankin, Andrew V / Daly, Roger J / Zhang, Xiaohui / Mukhopadhyay, Debabrata. ·Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, Rochester, MN 55905. · Bioengineering Program & Department of Mechanical Engineering and Mechanics, Lehigh University, Bethlehem, PA 18015. · The Kinghorn Cancer Centre, Cancer Research Division, Garvan Institute of Medical Research, 370 Victoria St, Darlinghurst, Sydney, NSW 2010, Australia. · Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, NSW 2200, Australia. · South Western Sydney Clinical School, Faculty of Medicine, University of NSW, Liverpool NSW 2170, Australia. · Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia. ·Cancer Res · Pubmed #23689123.

ABSTRACT: Metastasis, the leading cause of cancer death, requires tumor cell intravasation, migration through the bloodstream, arrest within capillaries, and extravasation to invade distant tissues. Few mechanistic details have been reported thus far regarding the extravasation process or re-entry of circulating tumor cells at metastatic sites. Here, we show that neuropilin-2 (NRP-2), a multifunctional nonkinase receptor for semaphorins, vascular endothelial growth factor (VEGF), and other growth factors, expressed on cancer cells interacts with α5 integrin on endothelial cells to mediate vascular extravasation and metastasis in zebrafish and murine xenograft models of clear cell renal cell carcinoma (RCC) and pancreatic adenocarcinoma. In tissue from patients with RCC, NRP-2 expression is positively correlated with tumor grade and is highest in metastatic tumors. In a prospectively acquired cohort of patients with pancreatic cancer, high NRP-2 expression cosegregated with poor prognosis. Through biochemical approaches as well as Atomic Force Microscopy (AFM), we describe a unique mechanism through which NRP-2 expressed on cancer cells interacts with α5 integrin on endothelial cells to mediate vascular adhesion and extravasation. Taken together, our studies reveal a clinically significant role of NRP-2 in cancer cell extravasation and promotion of metastasis.

4 Article Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. 2012

Biankin, Andrew V / Waddell, Nicola / Kassahn, Karin S / Gingras, Marie-Claude / Muthuswamy, Lakshmi B / Johns, Amber L / Miller, David K / Wilson, Peter J / Patch, Ann-Marie / Wu, Jianmin / Chang, David K / Cowley, Mark J / Gardiner, Brooke B / Song, Sarah / Harliwong, Ivon / Idrisoglu, Senel / Nourse, Craig / Nourbakhsh, Ehsan / Manning, Suzanne / Wani, Shivangi / Gongora, Milena / Pajic, Marina / Scarlett, Christopher J / Gill, Anthony J / Pinho, Andreia V / Rooman, Ilse / Anderson, Matthew / Holmes, Oliver / Leonard, Conrad / Taylor, Darrin / Wood, Scott / Xu, Qinying / Nones, Katia / Fink, J Lynn / Christ, Angelika / Bruxner, Tim / Cloonan, Nicole / Kolle, Gabriel / Newell, Felicity / Pinese, Mark / Mead, R Scott / Humphris, Jeremy L / Kaplan, Warren / Jones, Marc D / Colvin, Emily K / Nagrial, Adnan M / Humphrey, Emily S / Chou, Angela / Chin, Venessa T / Chantrill, Lorraine A / Mawson, Amanda / Samra, Jaswinder S / Kench, James G / Lovell, Jessica A / Daly, Roger J / Merrett, Neil D / Toon, Christopher / Epari, Krishna / Nguyen, Nam Q / Barbour, Andrew / Zeps, Nikolajs / Anonymous1421514 / Kakkar, Nipun / Zhao, Fengmei / Wu, Yuan Qing / Wang, Min / Muzny, Donna M / Fisher, William E / Brunicardi, F Charles / Hodges, Sally E / Reid, Jeffrey G / Drummond, Jennifer / Chang, Kyle / Han, Yi / Lewis, Lora R / Dinh, Huyen / Buhay, Christian J / Beck, Timothy / Timms, Lee / Sam, Michelle / Begley, Kimberly / Brown, Andrew / Pai, Deepa / Panchal, Ami / Buchner, Nicholas / De Borja, Richard / Denroche, Robert E / Yung, Christina K / Serra, Stefano / Onetto, Nicole / Mukhopadhyay, Debabrata / Tsao, Ming-Sound / Shaw, Patricia A / Petersen, Gloria M / Gallinger, Steven / Hruban, Ralph H / Maitra, Anirban / Iacobuzio-Donahue, Christine A / Schulick, Richard D / Wolfgang, Christopher L / Morgan, Richard A / Lawlor, Rita T / Capelli, Paola / Corbo, Vincenzo / Scardoni, Maria / Tortora, Giampaolo / Tempero, Margaret A / Mann, Karen M / Jenkins, Nancy A / Perez-Mancera, Pedro A / Adams, David J / Largaespada, David A / Wessels, Lodewyk F A / Rust, Alistair G / Stein, Lincoln D / Tuveson, David A / Copeland, Neal G / Musgrove, Elizabeth A / Scarpa, Aldo / Eshleman, James R / Hudson, Thomas J / Sutherland, Robert L / Wheeler, David A / Pearson, John V / McPherson, John D / Gibbs, Richard A / Grimmond, Sean M. ·The Kinghorn Cancer Centre, 370 Victoria Street, Darlinghurst, Sydney, New South Wales 2010, Australia. ·Nature · Pubmed #23103869.

ABSTRACT: Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.

5 Article RON is not a prognostic marker for resectable pancreatic cancer. 2012

Tactacan, Carole M / Chang, David K / Cowley, Mark J / Humphrey, Emily S / Wu, Jianmin / Gill, Anthony J / Chou, Angela / Nones, Katia / Grimmond, Sean M / Sutherland, Robert L / Biankin, Andrew V / Daly, Roger J / Anonymous2910736. ·Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, NSW 2010, Australia. ·BMC Cancer · Pubmed #22958871.

ABSTRACT: BACKGROUND: The receptor tyrosine kinase RON exhibits increased expression during pancreatic cancer progression and promotes migration, invasion and gemcitabine resistance of pancreatic cancer cells in experimental models. However, the prognostic significance of RON expression in pancreatic cancer is unknown. METHODS: RON expression was characterized in several large cohorts, including a prospective study, totaling 492 pancreatic cancer patients and relationships with patient outcome and clinico-pathologic variables were assessed. RESULTS: RON expression was associated with outcome in a training set, but this was not recapitulated in the validation set, nor was there any association with therapeutic responsiveness in the validation set or the prospective study. CONCLUSIONS: Although RON is implicated in pancreatic cancer progression in experimental models, and may constitute a therapeutic target, RON expression is not associated with prognosis or therapeutic responsiveness in resected pancreatic cancer.