CD147: Key Roles in Metabolism, Immunity, Cancer, and Viruses

CD147, also known as Basigin or EMMPRIN, is a multifaceted protein integral to various physiological and pathological processes. Its significance spans across fields such as metabolism, immunity, cancer research, and virology, making it a crucial subject of study for multiple disciplines.

Recent discoveries have underscored its diverse roles, implicating CD147 in cellular energy regulation, immune system modulation, tumor progression, and viral infection mechanisms. These insights are helping reshape our understanding of these complex biological systems and open new avenues for therapeutic interventions.

CD147 Structure and Function

CD147 is a transmembrane glycoprotein that plays a significant role in various cellular processes. Structurally, it is characterized by its immunoglobulin-like domains, which facilitate interactions with a wide range of ligands and proteins. This structural versatility allows CD147 to participate in numerous cellular functions, acting as a mediator in cell-to-cell communication and signaling pathways. The protein’s ability to form complexes with other membrane proteins further enhances its functional diversity, enabling it to influence cellular behavior in multiple contexts.

The glycosylation of CD147 is another aspect that contributes to its functional capabilities. Glycosylation affects the protein’s stability, localization, and interaction with other molecules. This post-translational modification is crucial for CD147’s role in modulating cellular responses and maintaining homeostasis. The dynamic nature of its glycosylation patterns allows CD147 to adapt to different physiological conditions, thereby influencing processes such as cell adhesion, migration, and proliferation.

In addition to its structural attributes, CD147’s function is also defined by its ability to interact with matrix metalloproteinases (MMPs). This interaction is particularly important in tissue remodeling and repair, as MMPs are involved in the degradation of extracellular matrix components. By regulating MMP activity, CD147 contributes to maintaining the balance between tissue breakdown and regeneration, which is essential for normal physiological function and response to injury.

Role in Cellular Metabolism

CD147 has emerged as a significant player in the regulation of cellular metabolism, a process fundamental to cellular growth and energy production. One of the notable ways CD147 influences metabolism is through its involvement in lactate transport. It functions alongside monocarboxylate transporters (MCTs), which are responsible for the export and import of lactate across cell membranes. Lactate, often a byproduct of anaerobic glycolysis, is not merely a waste product but also serves as a vital energy source for various tissues, including muscle and brain. By facilitating lactate transport, CD147 plays a part in maintaining metabolic homeostasis.

Beyond lactate transport, CD147’s role extends to the regulation of glucose metabolism. It has been observed to interact with glucose transporters, influencing their expression and activity. This interaction is particularly significant in cancer cells, which often rely on altered glucose metabolism for rapid energy production and growth. CD147’s impact on glucose transport can therefore be linked to the metabolic shifts seen in tumor cells, highlighting its potential as a target for cancer therapy.

The metabolic role of CD147 also intersects with its ability to influence mitochondrial function. Mitochondria are the powerhouses of the cell, generating ATP through oxidative phosphorylation. CD147 has been implicated in modulating mitochondrial activity, thereby affecting cellular energy levels and metabolic efficiency. This modulation is crucial in conditions where energy demand fluctuates, such as during cell proliferation or stress responses.

CD147 in Immune Response

CD147’s involvement in the immune response is both intricate and multifaceted, shaping how the immune system reacts to various challenges. One of its primary roles is in the recruitment and activation of immune cells. CD147 is known to influence the behavior of lymphocytes, a type of white blood cell crucial for immune defense. By modulating lymphocyte activity, CD147 contributes to the body’s ability to mount an effective immune response against pathogens. This modulation can affect how quickly and robustly the immune system reacts, impacting the overall efficacy of immune defenses.

The protein also plays a part in the inflammatory response, a vital component of the immune system’s strategy to combat infection and injury. CD147 is involved in the regulation of cytokine production, which are signaling molecules that help mediate and regulate immunity and inflammation. By influencing cytokine levels, CD147 helps orchestrate the inflammatory response, ensuring it is appropriately scaled to the threat level. This regulation is essential to prevent excessive inflammation, which can lead to tissue damage and chronic inflammatory diseases.

Moreover, CD147 has been implicated in the process of immune cell adhesion and migration. It assists immune cells in navigating through the body to sites of infection or injury, facilitating their movement across barriers such as blood vessel walls. This ability to enhance immune cell trafficking is critical for timely and effective immune surveillance and response.

CD147 in Cancer Progression

CD147’s involvement in cancer progression is a subject of significant interest due to its multifarious roles in tumor biology. This protein has been observed to contribute to the enhancement of cancer cell invasiveness and metastasis, processes that are central to cancer progression. It achieves this by interacting with various signaling pathways that promote the motility and survival of cancer cells. These interactions enable tumor cells to detach from their primary site, invade surrounding tissues, and eventually establish secondary tumors in distant organs.

The expression levels of CD147 have been correlated with tumor aggressiveness, making it a potential biomarker for assessing cancer prognosis. Elevated CD147 expression is often associated with poor outcomes, as it can drive the processes that lead to rapid tumor growth and dissemination. The ability of CD147 to influence angiogenesis, the formation of new blood vessels, further complicates its role in cancer. By promoting angiogenesis, CD147 ensures that growing tumors receive an adequate supply of nutrients and oxygen, facilitating their expansion.

CD147 in Viral Infections

CD147’s role in viral infections has garnered attention due to its involvement in the entry and replication of certain viruses. It serves as a receptor for several pathogens, facilitating their attachment and entry into host cells. This interaction is crucial for the viral life cycle, influencing how efficiently a virus can infect and spread within a host. The protein’s expression on the cell surface can be exploited by viruses, such as the human immunodeficiency virus (HIV) and others, to gain access to cells, making it a target of interest for developing antiviral strategies.

The modulation of CD147 expression during viral infections can affect the host’s immune response, potentially altering disease progression. Some viruses can upregulate CD147 on infected cells, enhancing viral replication and spread. This upregulation can also influence the host cell’s susceptibility to further infection, creating a feedback loop that exacerbates the viral burden. Understanding these interactions provides insights into how viruses manipulate host cell machinery and may inform the development of therapeutic interventions aimed at disrupting these processes.