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Pancreatic Neoplasms: HELP
Articles by Leanne Li
Based on 4 articles published since 2010
(Why 4 articles?)
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Between 2010 and 2020, Leanne Li wrote the following 4 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article GKAP Acts as a Genetic Modulator of NMDAR Signaling to Govern Invasive Tumor Growth. 2018

Li, Leanne / Zeng, Qiqun / Bhutkar, Arjun / Galván, José A / Karamitopoulou, Eva / Noordermeer, Daan / Peng, Mei-Wen / Piersigilli, Alessandra / Perren, Aurel / Zlobec, Inti / Robinson, Hugh / Iruela-Arispe, M Luisa / Hanahan, Douglas. ·Swiss Institute of Cancer Research, School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland. · David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. · Institute of Pathology, University of Bern, Murtenstrasse 31, 3008 Bern, Switzerland. · Institute of Pathology, University of Bern, Murtenstrasse 31, 3008 Bern, Switzerland; School of Life Science, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland. · Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK. · Department of Molecular, Cell and Developmental Biology, Jonsson Comprehensive Cancer Center and Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA. · Swiss Institute of Cancer Research, School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland. Electronic address: douglas.hanahan@epfl.ch. ·Cancer Cell · Pubmed #29606348.

ABSTRACT: Genetic linkage analysis previously suggested that GKAP, a scaffold protein of the N-methyl-D-aspartate receptor (NMDAR), was a potential modifier of invasion in a mouse model of pancreatic neuroendocrine tumor (PanNET). Here, we establish that GKAP governs invasive growth and treatment response to NMDAR inhibitors of PanNET via its pivotal role in regulating NMDAR pathway activity. Combining genetic knockdown of GKAP and pharmacological inhibition of NMDAR, we implicate as downstream effectors FMRP and HSF1, which along with GKAP demonstrably support invasiveness of PanNET and pancreatic ductal adenocarcinoma cancer cells. Furthermore, we distilled genome-wide expression profiles orchestrated by the NMDAR-GKAP signaling axis, identifying transcriptome signatures in tumors with low/inhibited NMDAR activity that significantly associate with favorable patient prognosis in several cancer types.

2 Article Autocrine, paracrine and necrotic NMDA receptor signalling in mouse pancreatic neuroendocrine tumour cells. 2017

Robinson, Hugh P C / Li, Leanne. ·Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK hpcr@cam.ac.uk. · David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02142, USA. ·Open Biol · Pubmed #29263248.

ABSTRACT:

3 Article Metabolic Symbiosis Enables Adaptive Resistance to Anti-angiogenic Therapy that Is Dependent on mTOR Signaling. 2016

Allen, Elizabeth / Miéville, Pascal / Warren, Carmen M / Saghafinia, Sadegh / Li, Leanne / Peng, Mei-Wen / Hanahan, Douglas. ·The Swiss Institute for Experimental Cancer Research (ISREC), EPFL SV ISREC, Station 19, 1015 Lausanne, Switzerland. · The Institute of Chemical Sciences and Engineering (ISIC-SB-EPFL), Ecole Polytechnique Fédérale de Lausanne, EPFL SB ISIC-Direction, CH A3 398 Station 6, 1015 Lausanne, Switzerland. · Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, CA 90095, USA. · The Swiss Institute for Experimental Cancer Research (ISREC), EPFL SV ISREC, Station 19, 1015 Lausanne, Switzerland; The Swiss Cancer Center Lausanne (SCCL), Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland. Electronic address: dh@epfl.ch. ·Cell Rep · Pubmed #27134166.

ABSTRACT: Therapeutic targeting of tumor angiogenesis with VEGF inhibitors results in demonstrable, but transitory efficacy in certain human tumors and mouse models of cancer, limited by unconventional forms of adaptive/evasive resistance. In one such mouse model, potent angiogenesis inhibitors elicit compartmental reorganization of cancer cells around remaining blood vessels. The glucose and lactate transporters GLUT1 and MCT4 are induced in distal hypoxic cells in a HIF1α-dependent fashion, indicative of glycolysis. Tumor cells proximal to blood vessels instead express the lactate transporter MCT1, and p-S6, the latter reflecting mTOR signaling. Normoxic cancer cells import and metabolize lactate, resulting in upregulation of mTOR signaling via glutamine metabolism enhanced by lactate catabolism. Thus, metabolic symbiosis is established in the face of angiogenesis inhibition, whereby hypoxic cancer cells import glucose and export lactate, while normoxic cells import and catabolize lactate. mTOR signaling inhibition disrupts this metabolic symbiosis, associated with upregulation of the glucose transporter GLUT2.

4 Article Hijacking the neuronal NMDAR signaling circuit to promote tumor growth and invasion. 2013

Li, Leanne / Hanahan, Douglas. ·Swiss Institute for Experimental Cancer Research, School of Life Science, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne 1015, Switzerland. ·Cell · Pubmed #23540692.

ABSTRACT: Glutamate and its receptor N-methyl-D-aspartate receptor (NMDAR) have been associated with cancer, although their functions are not fully understood. Herein, we implicate glutamate-driven NMDAR signaling in a mouse model of pancreatic neuroendocrine tumorigenesis (PNET) and in selected human cancers. NMDAR was upregulated at the periphery of PNET tumors, particularly invasive fronts. Moreover, elevated coexpression of NMDAR and glutamate exporters correlated with poor prognosis in cancer patients. Treatment of a tumor-derived cell line with NMDAR antagonists impaired cancer cell proliferation and invasion. Flow conditions mimicking interstitial fluid pressure induced autologous glutamate secretion, activating NMDAR and its downstream MEK-MAPK and CaMK effectors, thereby promoting invasiveness. Congruently, pharmacological inhibition of NMDAR in mice with PNET reduced tumor growth and invasiveness. Therefore, beyond its traditional role in neurons, NMDAR may be activated in human tumors by fluid flow consequent to higher interstitial pressure, inducing an autocrine glutamate signaling circuit with resultant stimulation of malignancy.