What is a Centromere?
The
centromere is a specialized region of the chromosome that plays a crucial role in cell division. It acts as the attachment point for spindle fibers during mitosis and meiosis, ensuring that each daughter cell receives an accurate copy of the chromosomes. The centromere is essential for the proper segregation of chromosomes and maintaining genomic stability.
The Role of Centromeres in Cancer
In the context of
cancer, centromeres are significant because their dysfunction can lead to chromosomal instability, aneuploidy, and ultimately tumorigenesis. Abnormal centromere function can result in improper chromosome segregation, leading to cells with an abnormal number of chromosomes, which is a hallmark of many cancers.
1.
Chromosomal Instability (CIN): Errors in centromere function can cause
chromosomal instability, which is linked to cancer progression. CIN can lead to the gain or loss of entire chromosomes, promoting genetic diversity within tumors and enabling the selection of more aggressive cancer cells.
2.
Aneuploidy: The incorrect segregation of chromosomes often results in
aneuploidy, a condition where cells have an abnormal number of chromosomes. Aneuploidy is frequently observed in cancer cells and is associated with poor prognosis.
3. Alteration in Centromere Proteins: Changes in the expression or function of centromere-associated proteins, such as CENP-A, CENP-B, and CENP-C, can disrupt centromere integrity. Overexpression or mutations in these proteins have been linked to various cancers.
1.
CENP-A: Overexpression of
CENP-A, a histone protein variant specific to centromeres, is often observed in several types of cancer, including breast, colorectal, and prostate cancers. CENP-A levels can serve as a prognostic marker for these cancers.
2.
Aurora Kinase B: This kinase is crucial for correct chromosome segregation. Elevated levels of
Aurora Kinase B are seen in many cancers and are linked to poor clinical outcomes.
3.
Survivin: This protein inhibits apoptosis and is involved in chromosome segregation during mitosis. High levels of
survivin are often found in cancer cells and are associated with resistance to chemotherapy.
1.
Aurora Kinase Inhibitors: These drugs inhibit
Aurora Kinase B, disrupting chromosome segregation and inducing apoptosis in cancer cells. Several Aurora kinase inhibitors are currently in clinical trials.
2. Histone Modifiers: Modifying the histone proteins at the centromere can affect chromosomal stability. Drugs targeting histone acetylation or methylation at centromeres are being explored for their anti-cancer potential.
3. Survivin Inhibitors: As survivin is overexpressed in many cancers, survivin inhibitors can induce apoptosis and increase the sensitivity of cancer cells to chemotherapy.
Conclusion
The centromere is a critical player in maintaining chromosomal stability. Its dysfunction can lead to chromosomal instability and aneuploidy, both of which are hallmarks of cancer. Understanding the role of centromeres in cancer has led to the identification of several biomarkers and potential therapeutic targets. Continued research in this area holds promise for developing new and effective cancer treatments.
