Research Task: The Cell Cycle & Uncontrolled Growth
- Christy Cheng
The cell cycle is a fundamental process that allows organisms to grow, repair tissues,
and reproduce. Understanding the intricate mechanisms that govern this cycle is crucial
to comprehending not only normal development but also the devastating consequences
of uncontrolled cell growth, such as cancer.
1.Cell proliferation
importance in growth - allows organisms to grow from a single cell to a complex multicellular
structure
→ eg. During early embryonic development, stem cells undergo rapid proliferation to form tissues
and organs of the body, which is essential for proper development and differentiation into
specialized cell types.
cell replacement - required by many tissues in the body constantly to maintain function and
integrity by continuously renewing through rapid proliferation
tissue repair - vital for repairing damaged tissues
→ eg. Wound healing: after a wound, keratinocytes (skin cells) proliferate to restore the epidermal
barrier. The healing process involves complex interactions between various cell types which
contribute to tissue regeneration and repair.
factors stimulating or inhibiting cell proliferation:
● stimulating factors: growth factors and nutrients can promote cell proliferation by
activating signaling pathways that lead to cell cycle entry
● inhibiting factors: contact inhibition, where cells stop dividing when they come into
contact with each other, and certain cytokines can inhibit proliferation
2.Phases of the cell cycle
The cell cycle consists of distinct phases: Interphase (G1, S, G2) and the Mitotic phase (M)
Interphase:
→ G1 Phase: The cell grows and synthesizes proteins necessary for DNA replication
→ S Phase: DNA replication occurs, resulting in two copies of each chromosome (sister
chromatids)
→ G2 Phase: The cell continues to grow and prepares for mitosis, ensuring all organelles are
duplicated and ready for division
Mitotic Phase (M): This phase includes mitosis (division of the nucleus) and cytokinesis (division
of the cytoplasm), resulting in two daughter cells with identical genetic material
3.Cell growth during interphase
interphase is significant for cell growth and preparation for division
checkpoints in the cell cycle (G1, G2, and M checkpoints) ensure that the cell is ready to proceed
to the next phase:
→ eg. the mitotic checkpoint confirms that all chromosomes are properly attached to the spindle
apparatus and aligned at the metaphase plate
1. G1 phase: cells increase in size, produce RNA, and synthesize proteins necessary for DNA
synthesis
➔ checkpoint - checks for DNA damage, cell size, nutrient availability, and growth signals to
proceed to the S phase
2. S phase: the primary activity is DNA replication, where the genetic material is duplicated
3. G2 phase: the cell undergoes further growth and prepares for mitosis by synthesizing
proteins required for chromosome segregation
➔ checkpoint - ensures that DNA replication has been completed accurately and checks for
DNA damage to move onto mitotic phase
4.Control of the cell cycle using cyclins
Cyclins: a family of proteins whose concentrations fluctuate throughout the cell cycle
Function: activate CDKs by binding to them, forming cyclin-CDK complexes that drive the cell
cycle forward
CDK (Cyclin-dependent kinases): a group of proteins kinases that are only active when bound to
a cyclin
Function: once activated, CDKs phosphorylate target proteins that are necessary for cell cycle
progression
Cyclin levels rise and fall at specific points in the cell cycle, influencing CDK activity. For
example, Cyclin D levels increase in response to growth signals, activating CDK4/6 to promote
progression from G1 to S phase.
The interaction between cyclins and CDKs is crucial for controlling specific transitions in the cell
cycle, such as the transition from G1 to S phase and G2 to M phase:
1. G1 Phase: Cyclin D binds to CDK4/6 to promote progression through G1.
2. S Phase: Cyclin E binds to CDK2 to facilitate DNA synthesis.
3. G2 Phase: Cyclin A binds to CDK2 and CDK1 for preparation for mitosis.
4. M Phase: Cyclin B binds to CDK1 (also known as Cdc2) to initiate mitosis.
Interaction Mechanism:
1. Binding: Cyclins bind to CDKs, causing a conformational change that activates the kinase
activity of CDKs
2. Phosphorylation: The activated cyclin-CDK complex then phosphorylates specific target
proteins, triggering various cell cycle events (e.g., DNA replication, mitosis)
3. Degradation: Cyclins are marked for degradation at the end of their function, which
inactivates the CDKs and allows the cell cycle to progress to the next phase
5.Consequences of mutations in genes that control the cell
cycle
Mutations in genes regulating the cell cycle can lead to uncontrolled cell growth, contributing to
cancer development.
Proto-oncogenes: These genes promote cell division. Mutations can convert them into oncogenes,
leading to excessive proliferation. For example, mutations in the Ras gene can lead to continuous
cell division.
Tumor Suppressor Genes: These genes normally inhibit cell division. Mutations can lead to loss of
function, allowing unchecked cell growth. A well-known example is the p53 gene, which plays a
critical role in preventing tumor formation by regulating the cell cycle and apoptosis.
→ Eg: The Rb gene (retinoblastoma) is a tumor suppressor that, when mutated, can lead to
retinoblastoma, a type of eye cancer. Similarly, mutations in p53 are found in many cancers,
highlighting its role in maintaining genomic stability
6.Differences between tumours
Benign Tumours:
● Non-cancerous and generally not life-threatening.
● Grow slowly and are usually encapsulated, making them well-defined.
● Do not invade surrounding tissues or metastasize to other parts of the body.
● Eg. lipomas (fat tissue) and adenomas (glandular tissue)
→ Characterized by slow cell division and growth. They may remain stable in size or grow very
slowly over time, often causing symptoms only when they compress adjacent structures
Malignant Tumours:
● Cancerous and can be life-threatening.
● Grow rapidly and lack a well-defined boundary, invading nearby tissues.
● Have the potential to metastasize, spreading to distant sites in the body.
● Examples include carcinomas (epithelial tissue) and sarcomas (connective tissue)
→ Exhibit rapid cell division and aggressive growth. They can double in size in a short period and
often lead to significant health issues due to their invasive nature
Malignant tumours can invade neighboring tissues and spread through several mechanisms:
1. Local Invasion: Cancer cells invade surrounding tissues by breaking down the extracellular
matrix using enzymes like matrix metalloproteinases (MMPs).
2. Intravasation: Cancer cells enter blood vessels or lymphatic vessels, gaining access to the
circulatory system.
3. Survival in Circulation: Tumour cells can survive in the bloodstream by forming aggregates
with platelets or evading immune detection.
4. Extravasation: Cancer cells exit the bloodstream at distant sites, aided by interactions with
the endothelial cells of blood vessels.
5. Colonization: Once in a new location, cancer cells can proliferate and establish secondary
tumours
Metastasis: the process by which cancer cells spread from the primary site of the tumour to distant
sites in the body, forming secondary tumours. This process is a hallmark of malignant tumours
and significantly complicates treatment
Factors that contribute to the metastatic potential of tumour cells:
● Genetic Mutations: Changes in genes that regulate cell adhesion, mobility, and survival can
enhance the ability of cancer cells to metastasize.
● Microenvironment: The surrounding tissue environment can influence cancer cell behavior;
certain tissues may provide favorable conditions for growth.
● Angiogenesis: The ability of malignant cells to stimulate the formation of new blood vessels
supports their growth and spread.
● Immune Evasion: Malignant cells may develop mechanisms to evade the immune system,
allowing them to survive and proliferate in new locations
References:
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