Cell Cycle Control and Cancer Biology Notes

Learning Objectives

  • At the end of the topic, you will be able to:
    • Explain the mechanisms that control the cell cycle: signals and checkpoints.
    • Outline the key groups of genes involved in cell cycle control and key mutations linked with cancer: Proto-oncogenes & tumor suppressor genes.
    • Describe cell death – necrosis vs apoptosis.

Phases of the Cell Cycle

  • G1 Phase: Growth and preparation of chromosomes for replication.
  • S Phase: Synthesis of DNA and duplication of centrosome.
  • G2 Phase: Preparation for mitosis.
  • M Phase: Mitosis.

Regulation of the Cell Cycle

  • The cell cycle is strictly regulated to ensure cells only divide under favorable conditions.
  • Key Signals Include:
    • Whether more cells are needed.
    • The health status of the cell.
    • Presence of mutations that could lead to cancer.
  • Cells can arrest the cycle at several checkpoints to ensure:
    • Completeness of chromosome replication before entering mitosis.

Extracellular Signals Controlling Cell Division

  • Mitogens: Stimulate cell division by overcoming cell cycle "brakes".
  • Growth Factors: Promote cell growth by enhancing macromolecule synthesis and inhibiting degradation.
  • Survival Factors: Suppress apoptosis (programmed cell death).

Cell Cycle Checkpoints

  • G2 Checkpoint:
    • Checks if all DNA is replicated.
    • Checks if all DNA damage is repaired before entering mitosis.
  • M Checkpoint:
    • Ensures all chromosomes are correctly attached to the mitotic spindle.
    • Delays cell division until all chromosomes are correctly attached; prolonged activation can lead to apoptosis, which is targeted by some anti-cancer drugs.

Role of Protein Kinases in Cell Cycle Regulation

  • Protein kinases add phosphates to proteins, changing their activity through structural alterations.
    • Cyclins and Cyclin-Dependent Kinases (Cdks):
    • Cdks are inactive unless bound to cyclins.
    • Different cyclin-Cdk complexes trigger specific steps in the cell cycle.
    • Concentration of cyclins changes throughout the cell cycle (e.g., M-cyclin concentration increases during interphase and decreases during mitosis).

Functions of M-Cdk

  • M-cyclin + mitotic Cdk = M-Cdk complex.
  • Functions of M-Cdk include:
    • Inducing chromosome condensation.
    • Breaking down the nuclear envelope.
    • Forming the mitotic spindle, facilitating entry into M phase.

Other Cyclin-Cdk Interactions

  • S-Cdk: Triggers DNA replication during S phase by recruiting DNA polymerase.
  • Each cyclin-Cdk complex plays a unique role in the various phases of the cell cycle.

Cancer and Cell Cycle Control

  • Defects in Cell Cycle Control:
    • Mutations in Cdks and cyclins lead to deregulated cell cycle progression, increasing cancer risk through unchecked cell division.
    • Cancer results from a complex interplay of mutations, often starting from a single abnormal cell.
    • Two main categories of genes involved in cancer:
    • Proto-oncogenes: Promote cell division (e.g., Ras gene).
    • Tumor Suppressor Genes: Inhibit cell division (e.g., Brca1, Brca2).

Characteristics of Cancer Cells

  • Behavior:
    • Divide continually under appropriate conditions.
    • Heritable mutations passed to daughter cells.
    • Show a tendency to dedifferentiate and lose specialized functions.
    • Display a lack of contact inhibition, causing them to pile atop one another.
    • Induce angiogenesis, increasing blood supply.
    • High mutation rates and potential for invasiveness.
    • Ability to metastasize to new body locations.

Cell Death Mechanisms

  • Apoptosis (Programmed Cell Death):
    • Characterized by:
    • Controlled process without inflammation.
    • Involves changes like chromatin condensation, membrane blebbing, and nuclear collapse.
  • Necrosis:
    • Uncontrolled death leading to inflammation.

Importance of Cell Death

  • Critical for:
    • Proper development and maintaining organism integrity.
    • Eliminating cells with DNA damage or infected by viruses.
    • Balancing the growth of cells in the immune system.
    • Targeting cancerous cells.

Key Learning Points

  • Understanding cell cycle control, the role of CDKs and cyclins.
  • Recognizing tumor suppressor genes and proto-oncogenes.
  • Differentiating between apoptosis and necrosis in cell death.