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      • Record: found
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      Methylglyoxal, a glycolysis side-product, induces Hsp90 glycation and YAP-mediated tumor growth and metastasis

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          Abstract

          Metabolic reprogramming toward aerobic glycolysis unavoidably induces methylglyoxal (MG) formation in cancer cells. MG mediates the glycation of proteins to form advanced glycation end products (AGEs). We have recently demonstrated that MG-induced AGEs are a common feature of breast cancer. Little is known regarding the impact of MG-mediated carbonyl stress on tumor progression. Breast tumors with MG stress presented with high nuclear YAP, a key transcriptional co-activator regulating tumor growth and invasion. Elevated MG levels resulted in sustained YAP nuclear localization/activity that could be reverted using Carnosine, a scavenger for MG. MG treatment affected Hsp90 chaperone activity and decreased its binding to LATS1, a key kinase of the Hippo pathway. Cancer cells with high MG stress showed enhanced growth and metastatic potential in vivo. These findings reinforce the cumulative evidence pointing to hyperglycemia as a risk factor for cancer incidence and bring renewed interest in MG scavengers for cancer treatment.

          DOI: http://dx.doi.org/10.7554/eLife.19375.001

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          NIH Image to ImageJ: 25 years of image analysis.

          Lynda C. Schneider, Wayne S Rasband (2013)
          For the past 25 years NIH Image and ImageJ software have been pioneers as open tools for the analysis of scientific images. We discuss the origins, challenges and solutions of these two programs, and how their history can serve to advise and inform other software projects.
          Article 0 comments Cited 4147 times – based on 0 reviews     Review now
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            Heat shock proteins in cancer: chaperones of tumorigenesis.

            Stuart K. Calderwood, Md Khaleque, Douglas B. Sawyer … (2006)
            The heat shock proteins (HSPs) induced by cell stress are expressed at high levels in a wide range of tumors and are closely associated with a poor prognosis and resistance to therapy. The increased transcription of HSPs in tumor cells is due to loss of p53 function and to higher expression of the proto-oncogenes HER2 and c-Myc, and is crucial to tumorigenesis. The HSP family members play overlapping, essential roles in tumor growth both by promoting autonomous cell proliferation and by inhibiting death pathways. The HSPs have thus become targets for rational anti-cancer drug design: HSP90 inhibitors are currently showing much promise in clinical trials, whereas the increased expression of HSPs in tumors is forming the basis of chaperone-based immunotherapy.
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              Cellular energy stress induces AMPK-mediated regulation of YAP and the Hippo pathway

              Jung-Soon Mo, Zhipeng Meng, Young Kim … (2015)
              YAP (Yes-associated protein) is a transcription co-activator in the Hippo tumor suppressor pathway and controls cell growth, tissue homeostasis, and organ size. YAP is inhibited by the kinase Lats, which phosphorylates YAP to induce its cytoplasmic localization and proteasomal degradation. YAP induces gene expression by binding to the TEAD family transcription factors. Dysregulation of the Hippo-YAP pathway is frequently observed in human cancers. Here we show that cellular energy stress induces YAP phosphorylation, in part due to AMPK-dependent Lats activation, thereby inhibiting YAP activity. Moreover, AMPK directly phosphorylates YAP S94, a residue essential for the interaction with TEAD, thus disrupting the YAP-TEAD interaction. AMPK-induced YAP inhibition can suppress oncogenic transformation of Lats-null cells with high YAP activity. Our study establishes a molecular mechanism and functional significance of AMPK in linking cellular energy status to the Hippo-YAP pathway.
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                Author and article information

                Contributors
                Ralph DeBerardinis: Role: Reviewing editor
                Journal
                Journal ID (nlm-ta): eLife
                Journal ID (iso-abbrev): Elife
                Journal ID (hwp): eLife
                Journal ID (publisher-id): eLife
                Title: eLife
                Publisher: eLife Sciences Publications, Ltd
                ISSN (Electronic): 2050-084X
                Publication date (Electronic, pub): 19 October 2016
                Publication date Collection: 2016
                Volume: 5
                Electronic Location Identifier: e19375
                Affiliations
                [1 ]deptMetastasis Research Laboratory, GIGA-CANCER , University of Liège , Liège, Belgium
                [2 ]deptMass Spectrometry Laboratory, GIGA-Systems Biology and Chemical Biology , University of Liège , Liège, Belgium
                [3 ]deptGIGA Proteomic Facility , University of Liège , Liège, Belgium
                [4 ]deptLaboratory for Metabolism and Vascular Medicine, Department of Internal Medicine , Maastricht University , Maastricht, Netherlands
                [5 ]Cardiovascular Research Institute Maastricht , Maastricht, The Netherlands
                [6 ]deptLaboratory of Medicinal Chemistry - CIRM , University of Liège , Liège, Belgium
                [7 ]deptDepartment of Pathology, CHU , University of Liège , Liège, Belgium
                [8 ]deptLaboratory of Cellular and Tissular Biology, GIGA-Neurosciences , University of Liège , Liège, Belgium
                [9 ]deptLaboratory of Food and Biodynamics, Graduate School of Bioagricultural Sciences , University of Nagoya , Nagoya, Japan
                [10 ]deptDepartment of Chemistry , Yale University , New Haven, United States
                [11 ]deptSchool of Chemistry and Bio21 Molecular Science and Biotechnology Institute , University of Melbourne , Melbourne, Australia
                [12 ]Association for Research and Treatments Against Cancer , Paris, France
                [13]UT Southwestern Medical Center , United States
                [14]UT Southwestern Medical Center , United States
                Author notes
                Author information
                http://orcid.org/0000-0002-8796-2143
                Article
                Publisher ID: 19375
                DOI: 10.7554/eLife.19375
                PMC ID: 5081250
                PubMed ID: 27759563
                SO-VID: 26093ac4-9ee4-4612-94d9-7696ba39c082
                Copyright © © 2016, Nokin et al
                License:

                This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                Date received : 04 July 2016
                Date accepted : 17 October 2016
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100005627, Université de Liège;
                Award Recipient :
                MJN, FD and BCo are Télévie Fellows, BCh, ABl and AT are Télévie Post-Doctoral Fellows, PDT and ABe are Senior Research Associates, all from the National Fund for Scientific Research (FNRS, Belgium). This work was also supported by the Centre Anti-Cancéreux, University of Liège, Belgium. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
                Categories
                Subject: Cancer Biology
                Subject: Cell Biology
                Subject: Research Article
                Custom metadata
                elife-xml-version 2.5
                Author impact statement Carbonyl stress mediated by Methylglyoxal affects Hsp90 activity, inhibits the Hippo pathway and promotes tumor growth and metastasis in breast cancer.

                ScienceOpen disciplines: Life sciences
                Keywords: carbonyl stress,glyoxalase 1,lats1,breast cancer,methylglyoxal,yap,chicken,human,mouse
                Data availability:
                ScienceOpen disciplines: Life sciences
                Keywords: carbonyl stress, glyoxalase 1, lats1, breast cancer, methylglyoxal, yap, chicken, human, mouse

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