Lecture 5

• Student feedback does matter, so please complete your faculty of Arts and Science surveys as the course evaluations are used to improve your courses
• Professors can never see who wrote what in the surveys, and the department doesn't have access to the comments until way after the marks are due
• In the evening class, there are 385 students and the response rate is around 14%
• Entering the surveys is important for your future years, even though it doesn't decide everything
• Cancer


  An area of research where cells replicate out of control
• Greater than two out of every five Canadians will develop cancer during their lifetime, and one out of every four Canadians will die from cancer
• Worldwide, one in six deaths is due to cancer
• Cancer progression


  1. Cells divide out of control

  2. Cells break through the basal lamina

  3. Cells travel through the bloodstream

  4. Fewer than one in a thousand cells will survive to form metastasis

  5. Metastatic tumors grow in other organs
• About 5-10% of cancer deaths are due to the primary cancer, while 90-95% are due to metastases
• Epithelial cells


  Cells that cover external surfaces, organs, and line body cavities
• Cell junctions in epithelial cells

  • Tight junctions
  • Adherens junctions
  • Desmosomes
  • Gap junctions
  • Hemidesmosomes
• Tight junctions


  • Occluding junctions that seal neighboring cells together to prevent leakage of extracellular molecules between them, helping to polarize cells
• Adherens junctions


  • Cell-cell anchoring junctions that join actin bundles in one cell to similar bundles in the neighboring cell
• Desmosomes


  • Cell-cell anchoring junctions that join intermediate filaments in one cell to those in the neighboring cell
• Gap junctions


  • Form channels that allow small intracellular water-soluble molecules, including organic ions and metabolites, to pass from one cell to another
• Hemidesmosomes


  • Anchor intermediate filaments in a cell to the basal lamina
• The top three junctions (tight, adherens, desmosomes) help hold the sheet of epithelial cells together
• Mature epithelial cells are polarized, with cell junctions arranged in a specific order
• Tight junctions


  • Form a sealing strand along the region between two cells
• Adherens junctions


  • Often form adhesion belts along the region between two cells
• Desmosomes


  • Are spot-like cell-cell anchoring junctions, not forming belts like adherens junctions
• Tight junctions


  Create a tight seal between cells, prevent the mixing of the extracellular environments
• Tight junctions are composed of two transmembrane proteins called claudin and occludin
• Claudin in one cell interacts with claudin in the neighbouring cell, occludin in one cell interacts with occludin in the neighbouring cell
• Tight junctions prevent the diffusion of membrane proteins between the apical and basal sides of the cell
• Tight junctions form sealing strands along the region between two cells
• Adherens junctions


  Cell-cell anchoring junctions that link the actin cytoskeletons of neighbouring cells
• Desmosomes


  Cell-cell anchoring junctions that link the intermediate filament cytoskeletons of neighbouring cells
• Hemidesmosomes


  Cell-extracellular matrix anchoring junctions that link the intermediate filament cytoskeleton to the basal lamina
• Anchoring junctions provide mechanical strength to the epithelium
• Anchoring junctions


  • Transmembrane adhesion proteins link to either neighbouring cells or the extracellular matrix, intracellular linker proteins link the adhesion proteins to the cytoskeleton
• Adherens junctions


  Transmembrane adhesion proteins are classical cadherins, link to actin cytoskeleton
• Desmosomes


  Transmembrane adhesion proteins are non-classical cadherins (desmogleins and desmocollins), link to intermediate filament cytoskeleton
• Hemidesmosomes


  Transmembrane adhesion proteins are integrins, link to intermediate filament cytoskeleton and extracellular matrix
• Hemidesmosomes are not half a desmosome, the proteins that make them up are different
• As epithelial cells develop, adherens junctions form where the cells touch each other, concentrating the cadherin adhesion proteins
• Desmosomes


  Junctions that link to intermediate filaments, such as keratin filaments, and connect to a neighboring cell
• Hemidesmosomes


  Junctions that anchor keratin filaments to the basal lamina
• Hemidesmosomes are not half a desmosome, the proteins that make them up are very different
• Desmosomes


  • Transmembrane adhesion proteins are cadherin family members (non-classical cadherins like desmoglein and desmocollin)
  • Intracellular linker proteins (desmoplakin, plakophilin) link to keratin filaments