CENP-E, or Centromere-associated protein E, is a motor protein that plays a crucial role in chromosome alignment and segregation during cell division. Specifically, it is a kinesin-like protein that is essential for the proper functioning of the mitotic spindle, which ensures chromosomes are accurately distributed to daughter cells. CENP-E is pivotal in the metaphase to anaphase transition during mitosis.
In normal cells, CENP-E ensures the chromosomes are correctly attached to the spindle microtubules through the kinetochores. This attachment is vital for the chromosomes to align at the metaphase plate before being segregated into daughter cells during anaphase. CENP-E's role is to facilitate the movement of chromosomes towards the spindle equator, ensuring accurate chromosome congression and alignment.
Cancer cells often exhibit
chromosomal instability (CIN), which can lead to aneuploidy—an abnormal number of chromosomes. CENP-E dysfunction can contribute to CIN by causing improper chromosome segregation. Overexpression or mutations in CENP-E have been observed in various types of cancer, including breast cancer, colorectal cancer, and
lung cancer. This suggests that CENP-E may play a role in the progression and development of these malignancies.
Given its critical role in mitosis, CENP-E is an attractive target for cancer therapy. Inhibitors of CENP-E can disrupt the mitotic process, leading to cell cycle arrest and apoptosis in rapidly dividing cancer cells. Several
CENP-E inhibitors have been developed and are undergoing preclinical and clinical evaluations. These inhibitors aim to exploit the dependency of cancer cells on CENP-E for proliferation, thereby selectively targeting malignant cells while sparing normal cells.
While targeting CENP-E holds promise, there are challenges to consider. One major challenge is the potential for toxicity in normal cells, particularly those that rapidly divide, such as bone marrow and gastrointestinal cells. Additionally, cancer cells can develop resistance to CENP-E inhibitors, necessitating combination therapies or the development of next-generation inhibitors. Further research is needed to refine these therapies and minimize adverse effects.
Research on CENP-E in cancer is ongoing and has shown promising results in preclinical models. Clinical trials are exploring the efficacy and safety of CENP-E inhibitors in various cancers. The focus is on understanding the molecular mechanisms of CENP-E in cancer cells, identifying biomarkers for patient stratification, and optimizing therapeutic regimens. Advances in this field could lead to more effective and targeted cancer treatments.
Conclusion
CENP-E is a critical protein involved in chromosome segregation during cell division, and its dysfunction can contribute to cancer progression. As a potential target for cancer therapy, CENP-E inhibitors offer a promising avenue for selective cancer treatment. However, challenges remain in ensuring the specificity and efficacy of these inhibitors while minimizing toxicity. Ongoing research and clinical trials will determine the future of CENP-E-targeted therapies in cancer treatment.
