The CENPF protein, also known as Centromere Protein F, is a large protein found within human cells. It is a component of the nuclear matrix and plays a role in various cellular activities.
The Role of CENPF in Healthy Cells
The CENPF protein functions in human cells by participating in cell division, known as mitosis. During the G2 phase of the cell cycle, a period of rapid protein synthesis, CENPF is part of the nuclear matrix. In late G2, it becomes part of the kinetochore, a protein complex that allows sister chromatids to attach to microtubules. These microtubules form the spindle apparatus, pulling the sister chromatids apart during cell division.
CENPF remains associated with the kinetochore through early anaphase. It then relocates to the spindle midzone and later to the intercellular bridge during telophase. This ensures accurate chromosome segregation. Beyond mitosis, CENPF also helps orient microtubules to form cellular cilia and regulates plasma membrane recycling by linking vesicles to the microtubule network.
CENPF’s Involvement in Disease
Dysregulation or mutations in the CENPF protein can contribute to several health conditions. Overexpression or underexpression of CENPF is linked to various types of cancer, indicating its role in tumor development and progression. For example, CENPF is frequently overexpressed in hepatocellular carcinoma (HCC), where higher levels correlate with a poorer prognosis. In breast cancer, elevated CENPF expression is associated with tumor bone metastasis.
In lung adenocarcinoma, CENPF is often highly expressed, correlating with advanced disease stage and a poorer prognosis. It is also upregulated in prostate cancer, contributing to malignant progression and serving as a marker for tumor cell proliferation. Beyond cancers, mutations in CENPF are implicated in developmental disorders like microcephaly and certain ciliopathies. For instance, CENPF mutations can impair cell division during early development, leading to conditions such as Stromme syndrome, characterized by features like cerebellar vermis hypoplasia and duodenal atresia.
CENPF as a Focus in Medical Research
CENPF is a focus in medical research due to its potential as a biomarker and therapeutic target. Its altered expression in various cancers makes it a candidate for diagnosing diseases or predicting progression. For instance, elevated CENPF expression is linked to a less favorable prognosis in hepatocellular carcinoma. Similarly, in melanoma, high CENPF levels are associated with poorer survival rates, suggesting its utility as a prognostic biomarker.
Researchers are also exploring CENPF as a therapeutic target, particularly in cancer. Studies show that silencing CENPF can inhibit cancer cell proliferation, migration, and invasion, and induce cell cycle arrest. For example, inhibiting CENPF reduces tumor cell growth in pancreatic cancer. A small molecule inhibitor, lonafarnib, which targets CENPF, is also being investigated as a potential drug to reduce cell proliferation, offering a promising avenue for developing new interventions.