SEMA7A is a protein found throughout the human body, belonging to the semaphorin family. While this family was initially recognized for its role in nerve cell development, SEMA7A (also known as CD108) plays broader roles. It participates in various biological processes, including those related to the immune system and other developmental pathways, offering insights into normal bodily operations and health conditions.
The Nature of SEMA7A
SEMA7A is classified as a glycosylphosphatidylinositol (GPI)-anchored protein, meaning it is attached to the cell membrane through a lipid linkage. Its structure includes a large, conserved “sema” domain and a plexin–semaphorin–integrin (PSI) domain.
These elements allow SEMA7A to interact with other molecules on cell surfaces. SEMA7A primarily engages with two main types of receptors: plexins, specifically plexin C1, and integrins, such as alpha-1 beta-1 (α1β1) integrin. The interaction between SEMA7A and these receptors, particularly plexin C1, involves the sema domains. These interactions mediate signals that influence cellular behavior.
SEMA7A’s Physiological Functions
SEMA7A plays diverse roles in maintaining normal bodily functions, particularly within the immune and nervous systems. In the immune system, SEMA7A is expressed on activated lymphocytes and thymocytes, helping regulate T-cell activation. It can either promote or suppress inflammation depending on the cell type and receptor it binds. For instance, SEMA7A can stimulate monocytes to produce pro-inflammatory cytokines through α1β1-integrins, but it can also induce anti-inflammatory responses by promoting interleukin-10 (IL-10) production in intestinal macrophages.
In the nervous system, SEMA7A contributes to neuronal development, including axon guidance and synapse formation. It was identified for its role in directing nerve fiber growth. Beyond these systems, SEMA7A is also involved in other developmental processes such as organogenesis and vascular growth. Its presence on various cell types, including keratinocytes in the skin and cells in the testis and gastrointestinal tract, indicates its widespread involvement in maintaining tissue homeostasis.
SEMA7A in Disease Pathways
Dysregulation of SEMA7A contributes to the development and progression of various diseases, particularly in cancer and inflammatory conditions. In cancer, elevated SEMA7A expression is observed in several tumor types, including breast cancer, glioblastoma, and oral cancer. It promotes tumor growth, invasion, and metastasis, potentially by signaling through integrin-β1 receptors. SEMA7A can also influence the tumor microenvironment by recruiting macrophages that foster angiogenesis, the formation of new blood vessels that supply tumors.
SEMA7A is also implicated in inflammatory conditions, exhibiting both pro- and anti-inflammatory effects depending on the context. It contributes to chronic inflammation by inducing pro-inflammatory cytokine production in macrophages and monocytes. In autoimmune diseases like rheumatoid arthritis and psoriasis, SEMA7A’s abnormal expression can exacerbate inflammation. SEMA7A is also being investigated for its role in neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease, where neuroinflammation is a factor.
Exploring SEMA7A for Health Applications
Understanding SEMA7A’s multifaceted roles in health and disease opens avenues for its potential health applications. SEMA7A shows promise as a therapeutic target, particularly in cancer and inflammatory diseases. Developing drugs that modulate its activity could offer new treatment strategies. For example, in breast cancer, SEMA7A has been identified as a potential target to overcome resistance to endocrine therapies.
Beyond therapeutics, SEMA7A also holds potential as a biomarker for disease diagnosis, prognosis, and monitoring treatment response. Its elevated expression has been linked to shorter survival in breast cancer patients and could indicate resistance to certain therapies. Research is ongoing to explore SEMA7A’s utility in predicting disease outcomes and guiding clinical decisions.