LESSON 1. Organization of the plasma membrane and its involvement in cell signaling
Protein and lipid composition of the plasma membrane and its organization in microdomains. Caveolae and lipid rafts. Alterations in cancer.
LESSON 2. Membrane receptors I. Types. Family Erb/HER.
Principal tyrosine kinase receptors. Structure and regulation of Erb/HER receptors. Receptor mutations in cancer.
LESSON 3. Membrane receptors II. Non-receptor tyrosine kinases.
Non-receptor tyrosine kinases: Src family. Signaling modules (SH2 and SH3 domains). Involvement in cancer.
LESSON 4. GPCR and Heterotrimeric G proteins: structure and activation.
G-protein coupled receptors (GPCR). Families Gq, Gi, G12/13, Gs. cAMP and cGMP as second messengers. Cellular responses mediated by cAMP and cGMP. The PKA pathway.
LESSON 5. Phospholipases and protein kinase C. Signaling domains.
PLA2 and PLC families of phospholipases. PKC protein families. Adaptor proteins and second messengers (DAG, PIP2, IP3).
LESSON 6. Small GTPases. Structure, processing and regulation I. Ras family.
Superfamily of Ras proteins, classification. Structure of Ras proteins and post-translational modifications. Regulation by GEFs and GAPs.
Main functions of Ras and Rap; involvement in tumoral processes. Germline Ras mutations: Noonan and Costello syndromes.
LESSON 7. Small GTPases. Structure, processing and regulation II. Rho family.
Rho family of GTPases. Regulation by GEFs, GAPs and GDIs. Main functions of Rho proteins: regulation of actin cytoskeleton. Implication in tumoral processes and other pathologies.
LESSON 8. MAPKs pathways.
MAPK families: ERK, p38 and JNK proteins. Regulation by phosphatases. Regulation by scaffold proteins. Agonists and inhibitors of the MAPK pathways. MAPKs in cancer.
LESSON 9. Lipid kinases: involvement in survival.
PI3K family and survival pathways. Regulation by phosphatases (PTEN). PI3K-Akt-mTor pathways in the regulation of mRNA translation. PI3K pathway and cancer.
LESSON 10. Calcium-mediated signaling.
Calcium as an intracellular messenger. Calcium receptors and calmodulin. Cellular calcium stores. Platelets, skeletal muscle and neurons as models of signaling by calcium.
LESSON 11. Signaling by hypoxia and reactive oxygen species (ROS).
Role of ROS in the regulation of signaling transduction and gene expression. Regulation of NADPH oxidases. Carcinogenesis by ROS. Hypoxia and tumor angiogenesis.
LESSON 12. Nuclear receptors and transcription factors. NFkB and JAK-STAT pathways.
Classification and general characteristics of the nuclear receptors-coupled signaling. JAK/STAT pathway. The NFkB pathway: interconnection between inflammation and cancer.
LESSON 13. Wnt and Notch pathways.
Regulation of cell polarity by the Wnt pathway. Mutations in cancer: colorectal adenocarcinoma as model. Role of vitamin D. The Notch pathway in the embryonic development. Deregulation in cancer.
LESSON 14. Cell death: apoptosis and autophagy pathways.
Extrinsic pathway (death receptors). Intrinsic pathway. Bcl-family of proteins. Caspases. Role of p38MAPKs.
LESSON 15. Adhesion and migration: cytoskeleton and focal adhesions proteins.
Cytoskeleton structures. Adhesion receptors (integrins). Actin polymerization and formation of adhesion and migration structures. Deregulation of adhesion and migration in metastasis.
LESSON 16. Cell cycle regulation.
Cell cycle phases. Cyclins and CDKs. CDKs inhibitors: INK4 family, CIP/KIP family. Retinoblastoma. P53. Cell cycle Checkpoints. Implications in DNA damage response.
LESSON 17. Cellular differentiation.
Differentiation versus proliferation. The hematopoietic lineage as a model. Epigenetics. Cancer stem cells.
LESSON 18. DNA damage repair. DNA repair pathways as targets for cancer therapy.
Types of DNA damage and DNA damage agents. Role of p53. Principal repair mechanisms: ATM and ATR pathways. Deregulation of the DNA damage response in cancer.