CELL SIGNALING IN CANCER

CELL SIGNALING IN CANCER

GRADO EN FARMACIA

1. Datos de la asignatura

(Fecha última modificación: 21-07-17 21:38)
Código
100166
Plan
201
ECTS
5.00
Carácter
OPTATIVA
Curso
4
Periodicidad
Segundo cuatrimestre
Área
MEDICINA
Departamento
Medicina
Plataforma Virtual

Campus Virtual de la Universidad de Salamanca

Datos del profesorado

Profesor
María Carmen Guerrero Arroyo
Grupo/s
1
Departamento
Medicina
Área
Medicina
Centro
Ctro. Investigación del Cáncer
Despacho
Lab. 17 Centro Investigación del Cáncer
Horario de tutorías

Monday to Friday. 12 to 14 h

URL Web
-
E-mail
cguerrero@usal.es
Teléfono
923 294 500 Ext. 4817

2. Sentido de la materia en el plan de estudios

Bloque formativo al que pertenece la materia.

AREA III: BIOLOGY

Linked courses: Biochemistry I, Biochemistry II, Biochemistry III, Molecular Biology

Papel de la asignatura.

Knowing the main signaling mechanisms and their components is essential to understand the physiological alterations in cells that lead to cancer and other pathologies. In the last 20-

30 years, discoveries in this field have experienced an exponential progression, which justifies the teaching of this matter as a specific subject. Cell Signaling in Cancer constitutes a subject complementary to others imparted in the Grade of Pharmacy, such as Biochemistry, Molecular Biology and Physiology. In addition, to know the signaling mechanisms of cells is essential for those students who want to follow a scientific career in Biomedicine.

Perfil profesional.

This course provides the knowledge to understand, at a molecular level, the mechanisms involved in the physiology of the cell, which are responsible for its correct homeostasis, as well as the alterations in these mechanims that might derive in a pathological phenotype. The course  provides  also  knowledge  for the  practice  of biomedical research  and  the development of activities in the following fields:

  • Industry and Distribution
  • Analysis and Public Health
  • Research and Teaching

3. Recomendaciones previas

The students must have basic knowledge in Biochemistry, Molecular Biology, Cell Biology and Genetics. Therefore, they must have passed the courses: “Biology”, imparted in first year and the three “Biochemistry” courses, imparted in first and second years.

4. Objetivo de la asignatura

  • To get a general view of the signaling mechanisms developed by cells from pluricelular organisms to communicate themselves and with their environment.
  • To know the main signaling transduction pathways at a physiological and pathological level.
  • To know the role of the main extracellular molecules, receptors, second messengers and intracellular proteins involved in these processes.
  • To be able to describe the main signaling pathways, the components involved, their regulatory mechanisms and the pathological implications of their disfunction with emphasis in the tumoral processes.
  • To know the main techniques and models used in cell signaling research.
  • To get a basic knowledge about the participation of the main signaling pathways in biological processes, such as proliferation and cell death, differentiation, response to hypoxia and to reactive oxygen species (ROS), adhesion and cell migration, etc. and their relationship with the tumoral disease.
  • To learn how to write an experimental report.
  • To learn how to discuss a scientific paper.

5. Contenidos

Teoría.

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.

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 scafold 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 a 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 oxydases. Carcinogenesis by ROS. Hypoxia and tumoral angiongenesis.

LESSON 12. Nuclear receptors and transcription factors. NFkB pathway.

Classification and general characteristics of the nuclear receptors-coupled signaling. JAK/STAT pathway. The NFkB pathway: interconextion 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. Desregulation 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.  

Adhesion receptors (integrins). Actin polymerization and formation of lamelipodia, filipodia and membrane ruffles. Role of Rho proteins. Deregulation of adhesion and migration in metastasis.

LESSON 16. Cellular differentiation.

Differentiation versus proliferation. The hematopoietic lineage as a model. Role of ROS in cell differentiation. Induction of differentiation as an antitumoral mechanism.

LESSON 17. Cell cycle regulation.

Cell cycle phases. Retinoblastoma. P53. Cyclins and CDKs. CDKs inhibitors: INK4 family, CIP/KIP family. Cell cycle Checkpoints. Implications in DNA damage response.

LESSON 18. DNA damage repair. DNA repair pathways as targets for cancer therapy.

Types of DNA damage. Role of p53. Principal repair mechanisms: ATM and ATR pathways. DNA damage agents and damage repair inhibitors in cancer treatment.

6. Competencias a adquirir

Básicas / Generales.

GC-1: Handling theoretical contents

GC-2: Handling methodology

GC-3: Basic abilities on information technologies

GC-4: Team work

GC-5: Ethics and moral integrity

Específicas.

EC-1: Skill competences: Ability to design experimental approaches to monitorize the activity of signaling pathways. Ability to present and discuss a scientific paper. Ability to perform standard techniques requiered in cell biology research.

EC-2: Knowledge competences: To know the principal mechanisms that regulate cell growth, cell differentiation and malignant transformation.

EC-3: Attitude competences: imagination, personal effort and colaboration within a team.

EC-4: To understand, write and be able to express in English.

EC-5: Handling bibliography data bases

Transversales.

TC-1: Instrumental: Troubleshooting. Decision making.

TC-2: Personal: Ability for criticism and self-criticism.

TC-3: Systemic: Ability to adapt to new situations.

7. Metodologías

Theoretical contents (18 lessons distributed in 27 master classes)

Practical contents:

  • Laboratory practicum: Monitorization of the ERK pathway in serum-stimulated fibroblasts by immunoblotting. Monitorization of cell adhesion to fibronectin by labeling with calcein AM.
  • Seminars: Extension of the lessons contents. Techniques applied to research in cell signaling. Journal clubs.

8. Previsión de Técnicas (Estrategias) Docentes

9. Recursos

Libros de consulta para el alumno.

Alberts, B. et al. Molecular Biology of the Cell (Fifth Edition). Garland Science, 2007

Lodish, H. et al. Molecular Cell Biology (Sixth Edition). Scientific American Books, 2007

Pollard TD, Earnshaw WC. Cell Biology (Second Edition). Elsevier, 2007

John Nelson. Structure and Function in Cell Signaling. John Wiley & Sons Ltd, 2008

Otras referencias bibliográficas, electrónicas o cualquier otro tipo de recurso.

Nature Reviews Journal (Molecular Cell Biology, Drug Discovery, Cancer, etc.) The Signaling Gateway: http://www.signaling-gateway.org

Recomended web-pages: Journals specialized in signaling transduction.           

10. Evaluación

Consideraciones generales.

Laboratory  practicum:

  • Mandatory attendance to laboratory practicum and seminars. Mandatory peformance of announced seminars (neccesary conditions to pass the matter).
  • A laboratory work notebook is required

Continuous  evaluation:

  • Participation in theoretical classes and seminars.
  • Fulfillment of at least two writtren control tests.

Global evaluation proof about the competences to be adquired in the course

It will deal with the contents of the theoretical classes, seminars and, in general, with the competences to achieve. It will last 2-3 hours

Criterios de evaluación.

To pass the matter it will be necessary

To get a qualification equal or superior to five, applying the criteria specified below

The global qualification will be obtain by calculating the weighted average following these criteria

1. Continous evaluation: 5%.

  • Participation in the master classes and seminars.
  • Written control tests.

2. Preparation and exposition of seminars: 20% .

3. Laboratory practicum: 15%.

  • Performing of laboratory work
  • Interest and comprehension of the lab work.
  • Evaluation of the notebook.

4. Global evaluation test of the competences to be adquired in the course 60%.

 

Instrumentos de evaluación.

Described in the above section.

 

Recomendaciones para la evaluación.

Study, consult of questions, handling of bibliographic resources (books and internet), team work.

Recomendaciones para la recuperación.

Practicum:

  • It is not repeated in the next course.
  • There is a possibility to improve the qualification of the practicum in the following courses by performing a new written test about the content of the practicum.              

Extraordinary Call: Evaluation

The global qualification will be obtain by calculating the weighted average following these criteria:

  • Continous evaluation: 5%.
  1. Participation in the master classes and seminars.
  2. Written control tests.
  • Preparation and exposition of seminars: 20%
  • Laboratory practicum: 15%.
  1. Performing of laboratory work
  2. Interest and comprehension of the lab work.
  3. Evaluation of the notebook.
  • Global evaluation test of the competences to be adquired in the course 60%.

11. Organización docente semanal