SlideServe
Télécharger Obtenir Pro
Menu
Accueil Pro
Préférences
ApparenceLight Aide et commentaires
© SlideServe · v2026

Signalling in tumor cells

kawena avatar
kawena
18 diapositives · 383 Views · Jan 11, 2013

Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s P rogrammes at the University of Pécs and at the University of Debrecen Identification number : TÁMOP-4.1.2-08/1/A-2009-0011.

#fly #carbon microphone #zofia kossak-szczucka #balancing network #hybrid balance #load #drag #oppose
Signalling in tumor cells - slide 1
01 / 18Signalling in tumor cells
1 / 17

Télécharger la présentation

Signalling in tumor cells
Une image / un lien ci-dessous est fourni (tel quel) pour télécharger la présentation

Politique de téléchargement : le contenu du site vous est fourni TEL QUEL pour votre information et votre usage personnel ; il ne peut être vendu, concédé sous licence ni partagé sur d’autres sites sans l’accord de son auteur.Le contenu vous est fourni TEL QUEL, pour votre information et votre usage personnel uniquement. Téléchargez la présentation en cliquant sur ce lien. Lors du téléchargement, si vous ne parvenez pas à télécharger une présentation, l’éditeur a peut-être supprimé le fichier de son serveur.Pendant le téléchargement, si vous ne parvenez pas à obtenir une présentation, le fichier a peut-être été supprimé par l’éditeur.

F I N

Plus de contenu associé

Transcription de la présentation

  1. Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat theUniversity of Pécs and at the University of Debrecen Identificationnumber: TÁMOP-4.1.2-08/1/A-2009-0011

  2. Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat theUniversity of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011 Tímea Berki and Ferenc Boldizsár Signaltransduction Signallingin tumor cells

  3. Immuneselectioninthedevelopment of cancer: no twotumorsarealike Initiation, proliferation, diversification Microevolution, selection of immune resistance Immune escape and unchecked proliferation

  4. Tumor and activated T cells Activated T cell Immune escape Tumor cell Cytokines Cytokinereceptors RCAS1 TCR MHC I RCAS1R Growtharrest CTLA4 B7-1/2 CD28 Proliferation Cell death FasL Fas FasL DcR3 DF3/MUC1

  5. WhathappenswhenFas-stimulatedimmunecellsresistto die? Cytokines? FasL Fas Tissue environment? Immunecells Tumor cells

  6. TGF-bsignalingin tumor signaling and cancerprogression Stromalcell Tumor cell LatentTGF- Proteases Thrombospondin Integrins Decorin Betaglycan ActiveTGF- Effectson tumor cells Effectsontumor environment Stroma Endothelial cells Immune cells ↓Fas-Lactivity ↓ NK cells ↓ T cells ↓ B cells ↑Proteases ↑ECM production Growth inhibition (early) Invasion (late) ↑Angiogenesis

  7. Type II Type I Fassignal FasL TPA Fas FADD FADD CAP3 CAP3 PKC DISC MAPK c-FLIP Caspase-8 tBid Bcl-2 Bcl-xL Cytc Cytc Caspase-9 Apaf-1 AIF Caspase-3 Caspase-8 Deathsubstrates APOPTOSIS

  8. Growth factors (GFs) • Small molecular weight soluble mediators • They control: • 1 Proliferation • 2 Survival • 3 Metabolism • 4 Tissue differentiation • Important implication in tumors • Cytokines – growth factors

  9. Receptortyrosinekinase(RTK)families • 90 unique Tyr kinases in the human genome, 58 are RTKs • Growth factor, cytokine and hormone receptors • Classes:

  10. GF signalingpathways Ligand RTK Dimerization P P P P P P P P GRB2 SOS PI3K PDK1 JAK PLC Ras Akt PKC Src Raf STAT Erk Proliferation Survival Migration Cell cycle progression Transcription

  11. GF receptorsastherapeutictargets EGF TGF β-cellulin Amphiregulin HB-EGF PDGF-C β-cellulin NRG2 NRG3 No specific ligands PDGF-B PDGF-D Heregulins VEGF-B VEGF-A VEGF-C VEGF-D PDGF-A SCF P P P P P P P P EGFR Her2 Her3 Her4 VEGFR1 VEGFR2 VEGFR3 PDGFR-a PDGFR-b c-kit P P P P P P P P P P P P P P P P P P GRB2 SOS Ras Rac CDC42 Rho P P P P P P P P P P P P P P P P P P ERK pathway JNK pathway p38 pathway Raf MEKK Tak PI3K Sorafenib Sirolimus P P P P P P P P P P P P P P P P P P Panitumumab Temsirolimus Erlotinib Midostaurin MEK1/2 MKK4/7 MKK3/6 P P P P P P P P P P P P P P P P P P Akt Gefitinib Motesanib Lapatinib Pazopanib Erk JNK p38 mTor Leflunomide Enzastaurin Trastuzumab Sunitinib Imatinib Vandetanib Everolimus Bevacizumab Cellsurvival Proliferation Apoptosisresistance Cetuximab Metastasis Angiogenesis

  12. HER genefamily • HER1/EGFR(1): ligandsknown (TNFa, EGF etc), kinaseactivity • HER2/EGFR2: no ligand, kinaseactivity • HER3/EGFR3:ligandsknown (TNFa, EGF etc), no kinaseactivity • HER4/EGFR4: ligandsknown, kinaseactivity • Characteristic:co-operations

  13. HER2 geneticsincancer

  14. Anti-EGFRresistancein NSCLC • EGFR resistancemutation 790M • K-RAS mutation • C-MET amplification • EGFR negativity (protein?)

  15. Colorectalcancer and EGFR • EGFR expression (mRNS and protein): 75-80% • Intensityvariable (1-100% cell) • EGFR amplification: 0.6-15% • Chr. 7 polisomy: 30% • Chr.7 LOH: 8% (loss) • TK-mutation: 12% (onlyAsia) • EC-LD R497K polimorphism • SP1-216 promoter G/T polimorphism

  16. VEGFR2 receptor signalinginendothelialcells VEGF-B VEGF VEGF-E VEGF-C VEGF-D P P P P P P VEGFR1 VEGFR2 VEGFR3 P P P P P P TSAd P P P P P P PLC Src GRB2 P P P P P P PKC Angiogenesis Monocytemigration Lymphangiogenesis PI3K Ca2+ Akt Raf SOS Ras Cellmigration MEK Caspase-9 Erk Bad eNOS Cellsurvival Vascularpermeability Cellproliferation

  17. Kinaseinhibitoryprofiles of anti-angiogenicagents Döme, Tímár, AntiCancerAgents, 2007

  18. Overview of EGF signaling EGF Vav2 EGFR PTP + E2Ub - - STAT1 STAT3 PLC H2O2 GRB2 Cbl IP3 NADPH synthesis DAG Gab1 SOS Targetgenes Shc Ca2+ + - - Cdc42 /Rac PKC Rac PI3K Ras Src DOK Targets PIP3 - Raf MEKK MEKK4 Akt PDK1 ADAM Ras GAP MAPKK MKK2 MKK4 Nck + GRB2 - Targets HB-EGF FAK Bad FKHR MAPK MAPK p38 JNK Gab1 Src PAK1 Paxillin C-Fos MAPK Shp2 RSK2 p53 Jun CAS WASP Rac JNK AP1 Apoptosis CREB Cell cycle Cytoskeleton