Tumour Suppressor Genes in Cancer – Definition, Role, Mechanism & Examples
Introduction
Cancer develops when the balance between cell division and cell death is lost. Among the key genetic players controlling this balance are tumour suppressor genes. These genes work as the body’s natural defense system against cancer by preventing uncontrolled cell growth. When tumour suppressor genes are mutated or inactivated, normal cells may transform into cancerous ones — giving rise to tumors.
In recent years, understanding tumour suppressor genes has become extremely important in cancer biology, diagnostics, and targeted therapy.
What Are Tumour Suppressor Genes?
Tumour suppressor genes (TSGs) are genes that protect cells from uncontrolled division and prevent tumour formation.
They act as “brakes” in the cell cycle.
Functions of Tumour Suppressor Genes
Tumour suppressor genes regulate several key cellular processes:
🔹 Control of cell cycle
🔹 DNA repair and genome stability
🔹 Induction of apoptosis (programmed cell death)
🔹 Suppression of metastasis
🔹 Regulation of cell differentiation
How Loss of Tumour Suppressor Genes Leads to Cancer
For a tumour suppressor gene to lose its function, both copies (alleles) of the gene must be inactivated — this is explained by Knudson’s Two-Hit Hypothesis.
Mechanisms of Inactivation
| Mechanism | Effect |
|---|---|
| Point mutation | Changes protein function |
| Gene deletion | Removes the gene completely |
| Epigenetic silencing | DNA methylation blocks gene expression |
| Chromosomal loss | Loss of chromosomal region carrying the gene |
| Viral oncogenes | Inhibit tumour suppressor proteins |
When tumour suppressor genes are lost, the cell cycle progresses uncontrollably, leading to tumour formation and cancer progression.
Types of Tumour Suppressor Genes
Tumour suppressor genes are classified based on their biological function:
| Type of TSG | Primary Role |
|---|---|
| Gatekeepers | Directly regulate cell proliferation and apoptosis |
| Caretakers | Maintain DNA stability and repair |
| Landscapers | Maintain normal cell–microenvironment interactions |
Major Examples of Tumour Suppressor Genes
| Gene | Normal Function | Associated Cancer When Mutated |
|---|---|---|
| TP53 (p53) | Cell cycle arrest, apoptosis, DNA repair | Breast, lung, colon, melanoma, etc. |
| RB1 (Retinoblastoma protein) | Blocks G1→S phase transition | Retinoblastoma, osteosarcoma |
| APC | Wnt signaling regulation | Colon cancer, familial adenomatous polyposis |
| BRCA1 / BRCA2 | Homologous recombination DNA repair | Breast and ovarian cancers |
| PTEN | Inhibits PI3K-AKT pathway | Endometrial, prostate, thyroid cancers |
| NF1 / NF2 | RAS pathway regulation | Neurofibromatosis and nervous-system tumors |
Tumour Suppressor Genes vs Proto-Oncogenes
| Feature | Tumour Suppressor Genes | Proto-Oncogenes |
|---|---|---|
| Role | Stop cell division | Stimulate cell division |
| Mutation Type | Loss of function | Gain of function |
| Mutation Requirement | Both alleles must be mutated | Single allele mutation is enough |
| Effect on Cancer | Loss causes cancer | Activation causes cancer |
Both are essential for maintaining normal cell growth; imbalance causes cancer.
Clinical Importance of Tumour Suppressor Genes
Diagnostic & Screening Tools
✔ Genetic mutation tests (e.g., TP53, BRCA1)
✔ Liquid biopsy for circulating tumour DNA
✔ Immunohistochemistry for protein expression patterns
Therapeutic Approaches
🔹 Gene therapy to restore tumour suppressor gene function
🔹 Targeted therapy for pathways activated due to gene loss (e.g., PARP inhibitors for BRCA loss)
🔹 Epigenetic therapy to reverse DNA methylation-driven inactivation
Recent Advances in Research
Modern cancer research focuses on:
🔬 CRISPR-based tumour suppressor gene restoration
🔬 Personalized medicine based on mutational signature
🔬 Immunotherapy linked with tumour suppressor gene status
These advances promise more precise and effective cancer treatments in the future.
Conclusion
Tumour suppressor genes are vital guardians of our genome. Their inactivation leads to genomic instability, uncontrolled growth, and ultimately cancer. A deeper understanding of tumour suppressor genes is revolutionizing cancer diagnostics, prevention, and targeted therapy. Future research and advanced gene-editing technologies hold hope for restoring these genes and preventing cancer progression.
