A

lecture 02/25

Session Overview

  • Purpose: Quick review and catch up with students who haven’t been called on.

  • Key topics for today: AE, AM, AG.

  • Announcements: Trigata resources available and upcoming study sessions posted on Piazza.

Cancer and Cell Regulation

  • Focus: Deregulated cell growth and migration associated with cancer.

  • Connection between cell cycle regulation and cancer can help in understanding growth processes.

Cell Signaling and Receptors

  • Different receptors can lead to varied outcomes despite activating the same second messenger (cyclic AMP).

  • Example:

    • Dictyostelium cells respond to cyclic AMP for migration.

    • Liver cells (e.g., glycogen-storing cells) respond to adrenaline, leading to cyclic AMP activation but resulting in different cellular actions.

  • Importance of understanding how similar signals result in different functionalities in various cell types.

Exploring Cell Growth

  • Investigating how changes in normal regulatory proteins can contribute to cancer development.

  • p53 Protein: Critical tumor suppressor that will be discussed in detail.

Analogy of Car Growth Regulation

  • Defects in a car's operation can be analogous to defects in cell growth regulation:

    • Stuck accelerator: Represents unregulated growth signals in cells.

    • Brake failure: Represents the loss of inhibitory signals in the cell cycle.

    • Importance of redundant systems (multiple brakes) in cell regulation as a safety mechanism against uncontrolled growth.

Diagram Interpretation

  • Diagrams connecting chromosomes, mRNA, and proteins to track signaling pathways:

    • Recognition of activating and inhibiting symbols in pathways.

    • Differentiation between activated versus inhibited pathways in cellular processes.

Pancreatic Cell Comparison

  • Analysis of healthy pancreatic cells and contrasting them with cancerous pancreatic cells:

    • Normal cells respond to social signals, instigating growth and division correctly.

    • In cancerous cells, mutations (e.g., always-active receptors) can lead to uncontrolled growth even without external signals.

Consequences of DNA Damage

  • Mechanisms by which cells detect DNA damage and respond accordingly:

    • Activation of proteins that can halt cell cycle progression (e.g., in s-phase) to allow for DNA repair.

    • Overactive p53 can lead cells into apoptosis, preventing the propagation of mutations.

  • Cancer cells may bypass these checkpoints, leading to proliferation with damaged DNA.

Role of p53 Protein

  • p53 defined:

    • Acts as a major cellular brake, preventing cell cycle progression with DNA damage.

    • Can function as a transcription factor to activate genes for DNA repair or promote apoptosis in heavily damaged cells.

  • Importance of p53 loss in many cancers leading to additional genetic instability.

Tumor Growth and Metastasis

  • Differentiation between benign tumors (localized growth) and malignant tumors (ability to invade and metastasize).

  • Angiogenesis: Formation of new blood vessels is essential for tumor survival and growth.

  • Cancer cells must:

    • Migrate to blood vessels or lymph nodes.

    • Invade surrounding tissues.

    • Promote angiogenesis to facilitate further growth.

Migration and Invasion Mechanisms

  • Actin polymerization is crucial for normal cell migration.

  • Tumor cells may exhibit uncontrolled actin dynamics contributing to metastasis.