2017/18
27148 - Molecular Basis of Cell Communication and Cancer
Optional
5.3. Syllabus
MOLECULAR BASIS OF CELL COMMUNICATION AND CANCER
Part I: Signal Transduction
1. Importance of cell communication in multicellular organisms. Pathways and mechanisms of cell communication. Transmitters, receptors and signal transduction. Main types of chemical messengers in higher animals. Chemical structure of messengers and action mechanism. Proteins as messengers: hormones and growth factors. Other messengers.
2. Small molecules and proteins involved in signal transduction. Membrane receptors. Cytoplasmic receptors. Nuclear receptors. Signal transmission from plasma membrane to nucleus: general mechanisms. Protein kinases and protein phosphatases. G-proteins. Importance of binding of covalent lipids. Second messengers.
3. Signaling through G protein-couled receptors. Heptaspanins (7TM receptors). Heterotrimeric G proteins. Adenylyl cyclase and cAMP. Protein kinase A (PKA) and AKAP. Generation of inositol trisphosphate (IP3) and diacylglicerol from PIP2. Phospholipases C (PLC). Ca++ as a second messenger: calmodulin. Protein kinase C (PKC) family. Receptors generating cGMP.
4. Survival and proliferative routes. Growth factor receptors. Signaling domains: SH2, SH3, PH, WW/WD. Other types of signaling domains. The MAP-kinases (MAPK) pathway. The PI3-kinase (PI3K) pathway. Protein kinase B/Akt (PKB/Akt). Signal transduction through insulin receptor. Growth-inhibitory signals: the TGF-b . Signal transduction and the cytoskeleton.
5. Cytokines. Cytokine families and biological effects. Properties of cytokines. Cytokine receptor families. Signal transduction: JAKs and STATs. Biotechnological applications of cytokines.
6. Steroid hormones and nuclear receptors. Hydrophobic messengers: steroid and non-steroid hormones. Structure and function of nuclear receptors. Homodimeric receptors. Heterodimeric receptors. Other signaling systems activating nuclear receptors: the Wnt/b-catenin pathway.
7. Signalling of cell death. Types of cell death: necrosis, programmed cell death or apoptosis. Apoptosis in Caenorhabditis elegans. Apoptosis in mammals. Extrinsic and intrinsic pathway of apoptosis. Apoptotic proteases: caspases. Bcl-2 superfamily proteins.
Part II: Molecular Basis of Cancer
8. The nature and origin of cancer. Characteristics of tumour cells. Cancer causes. Carcinogenic agents. Chemical carcinogenesis. Steps in the development of cancer. Risk factors and prevention of cancer.
9. Experimental models in cancer research. Cell cultures. Cell lines. Characterization of cell populations in tumour cell cultures. Animal xenografts. Biological parameters related to tumour progression. Usefulness and limitations of experimental models in cancer research.
10. Virus and cancer: discovery of oncogenes. Viral oncogenes. Cellular oncogenes. Human proto-oncogenes and oncogenes. The Src tyrosin kinase.
11. Growth factors, growth factor receptors and cancer. Growth factors and receptors (RTKs) involved in tumour pathogenesis. Autocrine growth factor (PDGF, TGF, IL-6) production and impairment of RTK function in human tumours (ErbB, ErbB2/Neu, Ret, Kit).
12. Disruption of cytoplasmic signalling circuitry in cancer. Cytoplasmic proteins involved in mitogenic signal transduction: Ras, Raf, Bcr-Abl. Transcription factors: PML-RAR, Myc.
13. Tumour-suppressor genes. Discovery of tumour-suppressor genes. Diversity of oncosuppressor genes and proteins. Retinoblastoma protein (Rb) and regulation of restriction entry point of cell cycle. Structure, function and action mechanism of p53 protein. The MDM2 and ARF proteins.
14. Cell-adhesion proteins involved in tumorigenesis. Tumour progression and extracellular matrix. Integrins. Tumour invasion and metalloproteases. Tumour angiogenesis.