What Is CD117? Its Role in Health, Disease, and Medicine
The c-Kit protein (CD117) is a key cell receptor that directs normal growth. Learn how its altered signaling contributes to disease and guides targeted therapies.
CD117, also known as c-Kit, is a protein on the surface of many cell types and is encoded by the KIT gene. It functions as a receptor, transmitting signals from outside the cell to the inside. These signals regulate processes like cell growth, division, and survival. Understanding CD117 provides insight into normal biological functions and the development of certain diseases.
The Biological Functions of CD117
CD117 is a receptor tyrosine kinase embedded in the cell membrane. Its primary role is to bind with a molecule called Stem Cell Factor (SCF). When SCF attaches to the CD117 receptor, it causes two CD117 proteins to pair up in a process called dimerization. This pairing activates the receptor’s internal kinase domain, which then triggers a cascade of signaling pathways inside the cell.
One of the main roles of CD117 is in the development of blood cells, a process called hematopoiesis. It is present on hematopoietic stem cells in the bone marrow, where its interaction with SCF promotes the survival and maturation of these cells into various types of blood and immune cells. Without this signaling, the production of new blood cells would be significantly impaired.
CD117 signaling is also necessary for the function of several other cell types:
- Mast cells: Immune cells involved in allergic reactions and inflammation.
- Melanocytes: Cells responsible for producing melanin, the pigment in skin and hair.
- Interstitial cells of Cajal (ICCs): These act as pacemakers for the gastrointestinal tract, generating rhythmic contractions to move food.
- Germ cells: The precursors to sperm and egg cells, involved in reproduction and fertility.
CD117 and Its Link to Disease
Alterations affecting the CD117 protein can lead to several diseases, particularly cancers. These changes often result from mutations in the KIT gene that cause the receptor to become permanently active, even without SCF. This constant signaling, known as a gain-of-function mutation, can drive cells to grow and divide uncontrollably, leading to tumor formation.
The most well-known disease associated with this mechanism is the gastrointestinal stromal tumor (GIST). These cancers arise from the interstitial cells of Cajal in the digestive tract. A large majority of these tumors are driven by KIT gene mutations that result in a constantly active CD117 receptor, causing the cells to proliferate.
KIT gene mutations are also implicated in certain types of blood cancers, particularly acute myeloid leukemia (AML). In a subset of AML cases, these mutations contribute to the uncontrolled growth of myeloid precursor cells in the bone marrow. This disrupts the normal production of blood cells and leads to the progression of the leukemia.
Another condition linked to CD117 dysfunction is mastocytosis. This is a rare disorder characterized by the abnormal accumulation of mast cells in tissues like the skin and bone marrow. The cause is frequently a gain-of-function KIT mutation that promotes excessive proliferation of mast cells. Other cancers, such as seminomas and some melanomas, have also been associated with KIT mutations.
Medical Applications Involving CD117
The discovery of CD117’s role in disease has led to advances in diagnostics and treatment. Because the protein is highly expressed in certain tumors, it serves as a diagnostic marker. Pathologists use a technique called immunohistochemistry to detect the presence of CD117 in a tissue sample, which helps identify GISTs and distinguish them from other abdominal tumors.
Beyond its use in diagnosis, CD117 has become a target for cancer therapy. This knowledge led to the development of drugs designed to block the aberrant signals from the CD117 receptor. These drugs are known as tyrosine kinase inhibitors (TKIs) and represent a form of targeted therapy.
The most prominent TKI is imatinib, which has significantly changed the treatment of GISTs. Imatinib works by fitting into the CD117 protein, blocking its kinase activity and shutting down the signaling that tells the cancer cell to grow. This targeted approach is also used in certain cases of AML and mastocytosis that have KIT mutations, demonstrating the broad impact of targeting this protein.