Signal Transduction
- YAP and TAZ are essential for basal and squamous cell carcinoma initiation
- Maud Debaugnies1,†,
- Adriana Sánchez‐Danés1,†,
- Sandrine Rorive2,
- Maylis Raphaël1,
- Mélanie Liagre1,
- Marie‐Astrid Parent1,
- Audrey Brisebarre1,
- Isabelle Salmon2 and
- Cédric Blanpain (cedric.blanpain{at}ulb.ac.be)*,1,3
- 1Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles, Brussels, Belgium
- 2Department of Pathology, Erasme University Hospital, University Libre de Bruxelles, Brussels, Belgium
- 3WELBIO, Université Libre de Bruxelles, Brussels, Belgium
- ↵*Corresponding author. Tel: +32 2555 4175; E‐mail: cedric.blanpain{at}ulb.ac.be
↵† These authors contributed equally to this work
The Hippo pathway transcription factors YAP and TAZ are expressed and active in basal and squamous cell carcinoma in mice and humans. Conditional deletion of YAP and TAZ in mouse models prevents skin cancer initiation.
Synopsis
The Hippo pathway transcription factors YAP and TAZ are expressed and active in basal and squamous cell carcinoma in mice and humans. Conditional deletion of YAP and TAZ in mouse models prevents skin cancer initiation.
YAP and TAZ are expressed in mouse and human basal and squamous cell carcinoma.
YAP and TAZ are mainly nuclear in basal and squamous cell carcinoma.
Basal and squamous cell carcinomas express YAP gene signatures.
Conditional deletion of YAP and TAZ prevents skin cancer initiation in mice.
EMBO Reports (2018) 19: e45809
- Received January 16, 2018.
- Revision received May 4, 2018.
- Accepted May 14, 2018.
- © 2018 The Authors
- Antagonistic interactions between two MAP kinase cascades in plant development and immune signaling
- Tongjun Sun1,†,
- Yukino Nitta1,†,
- Qian Zhang1,†,
- Di Wu1,
- Hainan Tian1,
- Jin Suk Lee2 and
- Yuelin Zhang (yuelin.zhang{at}ubc.ca)*,1
- 1Department of Botany, University of British Columbia, Vancouver, BC, Canada
- 2Department of Biology, Concordia University, Montreal, QC, Canada
- ↵*Corresponding author. Tel: +1 604 827 0076; E‐mail: yuelin.zhang{at}ubc.ca
↵† These authors contributed equally to this work
MAPKKK3/5 act upstream of MKK4/5 and MPK3/6 in PAMP‐triggered and DAMP‐triggered immunity in plants. The MAPK pathways specified by MAPKKK3/5 and the developmental YDA pathway antagonize by competing for downstream MKKs.
Synopsis
MAPKKK3/5 act upstream of MKK4/5 and MPK3/6 in PAMP‐triggered and DAMP‐triggered immunity in plants. The MAPK pathways specified by MAPKKK3/5 and the developmental YDA pathway antagonize by competing for downstream MKKs.
MAPKKK3/5, MKK4/5 and MPK3/6 form a MAPK cascade to transduce defence signals in PTI.
Developmental defects caused by silencing YDA are suppressed in the mapkkk3/5 double mutant.
Loss of YDA leads to increased PAMP‐induced activation of MPK3/MPK6.
Brassinosteroid has an inhibitory effect on PAMP‐induced MAPK activation.
EMBO Reports (2018) 19: e45324
- Received October 12, 2017.
- Revision received April 21, 2018.
- Accepted April 25, 2018.
- © 2018 The Authors
- CD36 initiates the secretory phenotype during the establishment of cellular senescence
- Mengyang Chong1,†,
- Tao Yin1,†,
- Rui Chen1,
- Handan Xiang1,
- Lifeng Yuan1,
- Yi Ding1,
- Christopher C Pan1,
- Zhen Tang1,
- Peter B Alexander1,
- Qi‐Jing Li (qi-jing.li{at}duke.edu)*,2 and
- Xiao‐Fan Wang (xiao.fan.wang{at}duke.edu)*,1
- 1Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA
- 2Department of Immunology, Duke University, Durham, NC, USA
- ↵*
Corresponding author. Tel: +1 919 668 4070; E‐mail: qi-jing.li{at}duke.edu
Corresponding author. Tel: +1 919 681 4861; E‐mail: xiao.fan.wang{at}duke.edu
↵† These authors contributed equally to this work
The scavenger receptor CD36 and its ligand amyloid beta trigger NF‐κB pathway activation and the acquisition of a senescence‐associated secretory phenotype (SASP) in response to various senescence‐inducing stimuli.
Synopsis
In response to various senescence‐inducing stimuli, normal mammalian cells rapidly upregulate the scavenger receptor CD36. Amyloid beta‐dependent CD36 signaling then triggers NF‐κB pathway activation, resulting in the production and secretion of numerous inflammatory proteins known to comprise the senescence‐associated secretory phenotype.
The multi‐ligand receptor CD36 is induced in multiple senescence contexts.
Amyloid beta activates CD36 to stimulate NF‐κB‐dependent cytokine and chemokine production.
Sustained secretory molecule production leads to the onset of a comprehensive senescent cell fate.
EMBO Reports (2018) 19: e45274
- Received October 2, 2017.
- Revision received March 8, 2018.
- Accepted March 23, 2018.
- © 2018 The Authors
- PRDM4 mediates YAP‐induced cell invasion by activating leukocyte‐specific integrin β2 expression
- Huan Liu1,†,
- Xiaoming Dai1,†,
- Xiaolei Cao1,†,
- Huan Yan1,
- Xinyan Ji1,
- Haitao Zhang1,
- Shuying Shen1,
- Yuan Si1,
- Hailong Zhang2,
- Jianfeng Chen2,
- Li Li3,
- Jonathan C Zhao4,
- Jindan Yu4,
- Xin‐Hua Feng1 and
- Bin Zhao (binzhao{at}zju.edu.cn)*,1
- 1Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang, China
- 2State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
- 3Institute of Aging Research, Hangzhou Normal University, Hangzhou, Zhejiang, China
- 4Department of Medicine‐Hematology/Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
- ↵*Corresponding author. Tel: +86 571 88208541; E‐mail: binzhao{at}zju.edu.cn
↵† These authors contributed equally to this work
Yes‐associated protein (YAP) is a transcriptional co‐activator and major effector of the Hippo pathway, promoting cell proliferation and stemness. YAP interacts with PRDM4, thereby promoting transendothelial invasion of cancer cells by inducing expression of the leukocyte‐specific integrin ITGB2.
Synopsis
Yes‐associated protein (YAP) is a transcriptional co‐activator and major effector of the Hippo pathway, promoting cell proliferation and stemness. YAP interacts with PRDM4, thereby promoting transendothelial invasion of cancer cells by inducing expression of the leukocyte‐specific integrin ITGB2.
PR/SET domain 4 (PRDM4) interacts with YAP to promote transcriptional activation of target genes.
PRDM4 and TEAD co‐ordinately mediate the activation of the YAP target gene ITGB2.
YAP‐induced ITGB2 expression promotes cancer cell invasion in a manner mimicking leukocytes.
EMBO Reports (2018) 19: e45180
- Received September 15, 2017.
- Revision received March 17, 2018.
- Accepted March 23, 2018.
- © 2018 The Authors
- EphrinB2/EphB4 signaling regulates non‐sprouting angiogenesis by VEGF
- Elena Groppa1,2,5,†,
- Sime Brkic1,2,†,
- Andrea Uccelli1,2,
- Galina Wirth3,
- Petra Korpisalo‐Pirinen3,
- Maria Filippova1,2,
- Boris Dasen1,2,
- Veronica Sacchi1,2,6,
- Manuele Giuseppe Muraro1,2,
- Marianna Trani1,2,
- Silvia Reginato1,2,
- Roberto Gianni‐Barrera1,2,
- Seppo Ylä‐Herttuala3,4 and
- Andrea Banfi (andrea.banfi{at}usb.ch)*,1,2
- 1Department of Biomedicine, University Hospital, University of Basel, Basel, Switzerland
- 2Department of Surgery, University Hospital, Basel, Switzerland
- 3A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland
- 4Heart Center, Kuopio University Hospital, Kuopio, Finland
- 5Present Address: The Biomedical Research Centre, The University of British Columbia, Vancouver, BC, Canada
- 6Present Address: Genomics Institute of the Novartis Research Foundation, San Diego, CA, USA
- ↵*Corresponding author. Tel: +41 61 265 3507; Fax: +41 61 265 3990; E‐mail: andrea.banfi{at}usb.ch
↵† These authors contributed equally to this work
EphrinB2/EphB4 signalling between pericytes and endothelium regulates the switch from normal to aberrant angiogenesis caused by increasing VEGF doses. Pharmacologic stimulation of EphB4 ensures exclusively physiological vessel growth under therapeutically relevant conditions of VEGF gene delivery.
Synopsis
EphrinB2/EphB4 signalling between pericytes and endothelium regulates the switch from normal to aberrant angiogenesis caused by increasing Vascular endothelial growth factor (VEGF) doses. Pharmacologic stimulation of EphB4 ensures exclusively physiological vessel growth under therapeutically relevant conditions of VEGF gene delivery.
The endothelial tyrosine kinase receptor EphB4 finely tunes the degree of endothelial proliferation by specific VEGF doses in vivo.
EphB4 does not affect VEGF‐R2 activation or internalization, but regulates its downstream signaling through p‐ERK1/2.
EphB4 stimulation limits the size of circumferential vessel enlargement induced by VEGF, thereby enabling splitting into normal capillaries and preventing aberrant growth into angiomas.
EMBO Reports (2018) 19: e45054
- Received August 23, 2017.
- Revision received March 3, 2018.
- Accepted March 8, 2018.
- © 2018 The Authors. Published under the terms of the CC BY NC ND 4.0 license
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
- PAWS1 controls Wnt signalling through association with casein kinase 1α
- Polyxeni Bozatzi1,†,
- Kevin S Dingwell2,†,
- Kevin ZL Wu1,
- Fay Cooper2,
- Timothy D Cummins1,
- Luke D Hutchinson1,
- Janis Vogt1,
- Nicola T Wood1,
- Thomas J Macartney1,
- Joby Varghese1,
- Robert Gourlay1,
- David G Campbell1,
- James C Smith (jim.smith{at}crick.ac.uk)*,2 and
- Gopal P Sapkota (g.sapkota{at}dundee.ac.uk)*,1
- 1Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, Dundee, UK
- 2The Francis Crick Institute, London, UK
- ↵*
Corresponding author. Tel: +44 20 3796 1103; E‐mail: jim.smith{at}crick.ac.uk
Corresponding author. Tel: +44 1382 386330; E‐mail: g.sapkota{at}dundee.ac.uk
↵† These authors contributed equally to this work
PAWS1 is a novel mediator of the Wnt signalling pathway through its interaction with and regulation of CK1α.
Synopsis
PAWS1 is a novel mediator of the Wnt signalling pathway through its interaction with and regulation of CK1α.
Microinjection of PAWS1 mRNA into Xenopus embryos causes complete axis duplication through the activation of Wnt signalling.
PAWS1‐knock‐out U2OS osteosarcoma cells exhibit diminished Wnt signalling, which can be rescued by the restoration of PAWS1.
PAWS1 interacts and co‐localizes with Ser/Thr protein kinase CK1α and the PAWS1 mutants incapable of binding CK1α fail to induce axis duplication and activate Wnt signalling.
The PAWS1:CK1α complex appears to control nuclear translocation of β‐catenin upon Wnt stimulation.
EMBO Reports (2018) 19: e44807
- Received July 12, 2017.
- Revision received February 5, 2018.
- Accepted February 8, 2018.
- © 2018 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Che‐1 is targeted by c‐Myc to sustain proliferation in pre‐B‐cell acute lymphoblastic leukemia
- Valentina Folgiero (valentina.folgiero{at}opbg.net)*,1,†,
- Cristina Sorino2,†,
- Matteo Pallocca2,
- Francesca De Nicola2,
- Frauke Goeman3,
- Valentina Bertaina1,
- Luisa Strocchio1,
- Paolo Romania1,
- Angela Pitisci1,
- Simona Iezzi2,
- Valeria Catena2,
- Tiziana Bruno2,
- Georgios Strimpakos4,
- Claudio Passananti5,
- Elisabetta Mattei4,
- Giovanni Blandino3,
- Franco Locatelli1,6,‡ and
- Maurizio Fanciulli (maurizio.fanciulli{at}ifo.gov.it)*,2,‡
- 1Department of Hematology/Oncology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
- 2SAFU, Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, Rome, Italy
- 3Oncogenomic and Epigenetic, Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, Rome, Italy
- 4CNR‐Institute of Cell Biology and Neurobiology CNR, IRCCS Fondazione Santa Lucia, Rome, Italy
- 5CNR‐Institute of Molecular Biology and Pathology, Department of Molecular Medicine, Sapienza University, Rome, Italy
- 6Department of Pediatric Science, University of Pavia, Pavia, Italy
- ↵*
Corresponding author. Tel: +39 0668593499; E‐mail: valentina.folgiero{at}opbg.net
Corresponding author. Tel: +39 0652662800; E‐mail: maurizio.fanciulli{at}ifo.gov.it
The RNA polymerase II‐binding protein Che‐1 is highly expressed at the onset of pediatric BCP‐ALL, but is down‐regulated with c‐Myc during remission. Che‐1 sustains c‐Myc‐dependent blast cells by directly regulating an overlapping set of cell proliferation genes.
Synopsis
The RNA polymerase II‐binding protein Che‐1 is highly expressed at the onset of pediatric BCP‐ALL, but is down‐regulated with c‐Myc during remission. Che‐1 sustains c‐Myc‐dependent blast cells by directly regulating an overlapping set of cell proliferation genes.
Che‐1/AATF is highly expressed in pediatric B‐cell precursor acute lymphoblastic leukaemia (BCP‐ALL).
Che‐1 expression is regulated by the oncogene c‐Myc.
Che‐1 is required for BCP‐ALL proliferation.
Che‐1 and c‐Myc control similar pathways, suggesting that Che‐1 is a downstream effector of c‐Myc.
EMBO Reports (2018) 19: e44871
- Received July 20, 2017.
- Revision received December 13, 2017.
- Accepted December 20, 2017.
- © 2018 The Authors
- Differential roles of ERRFI1 in EGFR and AKT pathway regulation affect cancer proliferation
- Junmei Cairns1,
- Brooke L Fridley2,3,
- Gregory D Jenkins2,
- Yongxian Zhuang1,
- Jia Yu1 and
- Liewei Wang (wang.liewei{at}mayo.edu)*,1
- 1Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA
- 2Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
- 3Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL, USA
- ↵*Corresponding author. Tel: +1 507 284 5264; E‐mail: wang.liewei{at}mayo.edu
The ERBB receptor inhibitor ERRFI1 regulates AKT/EGFR signaling in an EGFR‐dependent manner. In EGFR‐low cells, ERRFI1 activates AKT by blocking the PHLPP‐AKT interaction. In EGFR‐high cells, ERRFI1 functions as a negative regulator of the EGFR pathway.
Synopsis
The ERBB receptor inhibitor ERRFI1 regulates AKT/EGFR signaling in an EGFR‐dependent manner. In EGFR‐low cells, ERRFI1 activates AKT by blocking the PHLPP‐AKT interaction. In EGFR‐high cells, ERRFI1 functions as a negative regulator of the EGFR pathway.
In EGFR‐low cells, ERRFI1 activates AKT and promotes proliferation and chemotherapy resistance.
In EGFR‐low cells, AKT inhibition is beneficial and increases chemosensitivity.
In EGFR‐high cells, reduced ERRFI1 leads to active EGFR and increased cell proliferation.
In EGFR‐high cells, EGFR inhibition is beneficial and sensitizes for chemotherapy.
EMBO Reports (2018) 19: e44767
- Received July 5, 2017.
- Revision received December 12, 2017.
- Accepted December 18, 2017.
- © 2018 The Authors. Published under the terms of the CC BY NC ND 4.0 license
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
- Metabolic stress regulates ERK activity by controlling KSR‐RAF heterodimerization
- Amandine Verlande1,2,
- Michaela Krafčíková3,
- David Potěšil3,
- Lukáš Trantírek3,
- Zbyněk Zdráhal3,
- Moustafa Elkalaf4,
- Jan Trnka4,
- Karel Souček1,5,6,
- Nora Rauch7,8,9,
- Jens Rauch7,8,9,
- Walter Kolch7,8,9 and
- Stjepan Uldrijan (uldrijan{at}med.muni.cz)*,1,2
- 1International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic
- 2Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
- 3Central European Institute of Technology, Masaryk University, Brno, Czech Republic
- 4Laboratory for Metabolism and Bioenergetics, Third Faculty of Medicine, Charles University, Prague, Czech Republic
- 5Laboratory of Cytokinetics, Institute of Biophysics, Academy of Sciences, Brno, Czech Republic
- 6Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic
- 7Systems Biology Ireland, University College Dublin, Dublin, Ireland
- 8Conway Institute, University College Dublin, Dublin, Ireland
- 9School of Medicine, University College Dublin, Dublin, Ireland
- ↵*Corresponding author. Tel: +420 549494040; E‐mail: uldrijan{at}med.muni.cz
Somatic RAF/RAS mutations result in deregulated ERK signaling in melanomas. Metabolic stress impacts differently on ERK activation in BRAF‐ and NRAS‐mutant cells, indicating that targeting of energy metabolism is not a general therapeutic strategy for melanoma.
Synopsis
Somatic RAF/RAS mutations result in deregulated ERK signaling in melanomas. Metabolic stress impacts differently on ERK activation in BRAF‐ and NRAS‐mutant cells, indicating that targeting of energy metabolism is not a general therapeutic strategy for melanoma.
Metabolic stress induces CRAF/KSR dimerization in NRAS‐mutant cells, increasing ERK activity.
Metabolically stressed BRAFV600E‐mutant cells show an interaction of KSR with oncogenic BRAF.
High metabolic stress leads to the dissociation of mutant BRAF from KSR, reducing ERK activity.
Successful metabolic targeting strategies depend on the RAS/RAF mutational status.
EMBO Reports (2018) 19: 320–336
- Received May 23, 2017.
- Revision received November 15, 2017.
- Accepted November 24, 2017.
- © 2017 The Authors
- WDR11‐mediated Hedgehog signalling defects underlie a new ciliopathy related to Kallmann syndrome
- Yeon‐Joo Kim1,
- Daniel PS Osborn1,
- Ji‐Young Lee1,
- Masatake Araki2,
- Kimi Araki2,
- Timothy Mohun3,
- Johanna Känsäkoski4,
- Nina Brandstack4,
- Hyun‐Taek Kim5,8,
- Francesc Miralles1,
- Cheol‐Hee Kim5,
- Nigel A Brown1,
- Hyung‐Goo Kim6,
- Juan Pedro Martinez‐Barbera7,
- Paris Ataliotis1,
- Taneli Raivio4,
- Lawrence C Layman6 and
- Soo‐Hyun Kim (skim{at}sgul.ac.uk)*,1
- 1Molecular and Clinical Sciences Research Institute, St. George's, University of London, London, UK
- 2Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan
- 3Francis Crick Institute, London, UK
- 4Helsinki University Central Hospital, Helsinki, Finland
- 5Department of Biology, Chungnam National University, Daejeon, Korea
- 6Medical College of Georgia, Augusta University, Augusta, GA, USA
- 7Developmental Biology and Cancer Programme, Birth Defects Research Centre, UCL Great Ormond Street Institute of Child Health, London, UK
- 8Present Address: Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
- ↵*Corresponding author. Tel: +44 2082666198; E‐mail: skim{at}sgul.ac.uk
WDR11, the causative gene for congenital hypogonadotrophic hypogonadism and Kallmann syndrome, promotes Hedgehog singaling and ciliogenesis, linking these diseases to the human ciliopathy spectrum.
Synopsis
WDR11, the causative gene for congenital hypogonadotrophic hypogonadism and Kallmann syndrome, promotes Hedgehog singaling and ciliogenesis, linking these diseases to the human ciliopathy spectrum.
WDR11 functions as a novel element of the Hedgehog (Hh) signal pathway, which regulates fundamental aspects of mammalian development.
WDR11 shuttles between the nucleus and cytoplasm in response to Hh‐signaling.
WDR11 is required for the processing of GLI3 protein, forms a tertiary complex with EMX1 and GLI3 and regulates the expression of novel target genes EMX1/2 and GNRH1.
WDR11 is a cilia‐associated protein suggesting that CHH/KS with WDR11 mutations are ciliopathy disorders.
EMBO Reports (2018) 19: 269–289
- Received June 13, 2017.
- Revision received November 14, 2017.
- Accepted November 17, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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