CADM: A New Generation of Tumor Suppressor Genes
SummaryA tumor suppressor gene, also known as anti-onco gene, is an essential component of the body's defense against cancer. It usually facilitates apoptosis. With its absence, the human body will be functioning without its “brake” of cell proliferation. Cells are potent to go under abnormal growth processes and finally lead to tumor/cancer.
About Tumor Suppressor Genes
A tumor suppressor gene, also known as anti-onco gene, is an essential component of the body's defense against cancer. It usually facilitates apoptosis. With its absence, the human body will be functioning without its “brake” of cell proliferation. Cells are potent to go under abnormal growth processes and finally lead to tumor/cancer.
Here are some key features and functions of tumor suppressor genes:
Inhibition of Cell Growth: Tumor suppressor genes code for proteins that inhibit cell division and growth, acting as a control mechanism to prevent excessive cell proliferation.
DNA Repair: Many tumor suppressor proteins play a role in DNA repair, helping to correct genetic mutations and maintain the stability of the genome.
Cell Cycle Regulation: Tumor suppressors are involved in regulating the cell cycle, ensuring that cells only divide when necessary and that the process is tightly controlled.
Apoptosis Induction: They can trigger apoptosis, a process of programmed cell death, when a cell becomes irreparably damaged or poses a risk of becoming cancerous.
Senescence Promotion: Tumor suppressor genes can promote cellular senescence, a state in which cells stop dividing, preventing the replication of damaged DNA.
Cell Adhesion: Some tumor suppressor proteins are involved in maintaining cell adhesion, preventing cells from breaking away and spreading to other parts of the body (metastasis).
Introduction to CADM
Cell adhesion molecules are a diverse group of proteins that play a crucial role in mediating cell-to-cell interactions and cell-to-extracellular matrix interactions. They are involved in various cellular processes, including tissue development, immune responses, and maintenance of tissue integrity. Dysregulation of these molecules can lead to various diseases, including cancer metastasis, autoimmune disorders, and developmental abnormalities.
The molecules are found on the cell surface, where they facilitate adhesion to neighboring cells or the extracellular matrix, creating stable cell structures and supporting tissue organization. These molecules are essential for embryonic development, wound healing, immune cell recognition, and many other physiological functions.
Classification and Function
Among the superfamily of cell adhesion molecules, in this article, we mainly focus on Ig-Superfamily CADMs: the members of the Immunoglobulin superfamily of cell adhesion molecules, which play diverse roles in immune responses, neural development, and cell signaling.
Ig-Superfamily CADMs are named after the presence of one or more Immunoglobulin-like domains in their extracellular region, which are characteristic structural motifs found in antibodies. Ig-superfamily CADMs are involved in a wide range of biological processes and are critical for the development and functioning of various tissues and organs in the body.
Examples of Ig-superfamily CADMs include:
ICAM (Intercellular Adhesion Molecule):ICAMs are involved in immune responses and inflammation. They facilitate adhesion between leukocytes and endothelial cells, enabling leukocyte extravasation into tissues during inflammation.
NCAM (Neural Cell Adhesion Molecule): NCAM is crucial for neural development and plays a role in axon guidance, synapse formation, and neural plasticity.
VCAM (Vascular Cell Adhesion Molecule): VCAMs are involved in mediating the adhesion of leukocytes to vascular endothelial cells, facilitating the recruitment of immune cells during inflammation.
L1CAM (L1 Cell Adhesion Molecule): L1CAM plays a role in neural development, axon guidance, and cell migration.
PECAM-1 (Platelet Endothelial Cell Adhesion Molecule-1): PECAM-1 is expressed on the surface of platelets and endothelial cells and is involved in cell adhesion and signaling during immune responses.
Some key features and functions of Ig-superfamily CADMs include:
Cell Adhesion: Ig-superfamily CADMs are involved in mediating cell-to-cell adhesion, helping cells stick together and form tissues and organs. They play a vital role in tissue development, maintaining tissue integrity, and organizing complex cellular structures.
Immune Cell Interactions: Several Ig-superfamily CADMs are crucial for immune cell interactions. They facilitate the recognition and binding of immune cells, such as T cells, B cells, and antigen-presenting cells, during immune responses.
Neural Development: Certain Ig-superfamily CADMs are essential for neuronal development, axon guidance, and synapse formation in the nervous system. They play a role in establishing neural connections during brain development.
Cell Signaling: Ig-superfamily CADMs can transduce signals into cells, influencing various cellular processes, such as cell proliferation, differentiation, and survival. They often interact with other signaling molecules and receptors to regulate cellular activities.
Inflammation and Immune Responses: Some Ig-superfamily CADMs are involved in inflammatory responses, guiding leukocytes (white blood cells) to sites of inflammation or injury.
CADM is pivotal in governing numerous cellular functions, such as intercellular adhesion, cell motility, signal transduction, and immune regulation. Despite extensive research focused on exploring its role in tumor suppression, the precise in vivo function and molecular mechanisms underlying its tumor suppressor activity remain enigmatic.
CADM and Cancers
CADM1 and Tumor Immune Escape
In the process of tumor development, cancer cells can adopt various strategies to evade detection and destruction by the immune system, allowing them to grow and spread unchecked. CADM molecules, particularly CADM1, have been implicated in tumor immune escape due to their involvement in immune cell interactions and regulation of immune responses. Here's how CADM and tumor immune escape are interconnected:
Downregulation of CADM1 Expression: In some cancer types, CADM1 expression on the surface of tumor cells can be reduced or lost. CADM1 is involved in mediating interactions between cancer cells and immune cells, such as T cells and natural killer (NK) cells. Downregulation of CADM1 can weaken the adhesive interactions between tumor cells and immune cells, hindering the recognition and targeting of cancer cells by the immune system.
Inhibition of Immune Cell Activation: CADM1 can also participate in signaling pathways that regulate immune cell activation and function. Reduced CADM1 expression may lead to the dampening of immune cell responses, limiting their ability to identify and attack cancer cells effectively.
Immunosuppressive Microenvironment: Tumors can create an immunosuppressive microenvironment that hinders immune responses. CADM1 may be involved in modulating the immune cell composition within the tumor microenvironment, affecting the balance between pro-inflammatory and immunosuppressive factors. This can promote an environment in which immune cells are less effective at attacking tumor cells.
Disruption of Immune Synapses: CADM1 is crucial for the formation of immune synapses, specialized structures that facilitate interactions between immune cells and tumor cells. Disruption of these synapses, due to altered CADM1 expression or function, can impair immune cell communication and response, allowing tumor cells to escape immune surveillance.
Research into the relationship between CADM and tumor immune escape is still ongoing, and its complexities are not fully understood. However, understanding the roles of CADM molecules in tumor immune escape may offer valuable insights for developing novel immunotherapeutic strategies to overcome immune evasion and enhance the body's ability to recognize and eliminate cancer cells.
CADM1 and Lung Cancer
CADM1 is often downregulated or lost in lung cancer, particularly in non-small cell lung cancer (NSCLC). CADM1 acts as a tumor suppressor in the lung by inhibiting cell proliferation, promoting cell adhesion, and suppressing cancer cell migration and invasion. Its reduced expression can contribute to tumor progression and metastasis.
CADM1 and Ovarian Cancer
In ovarian cancer, CADM1 downregulation has been observed in certain subtypes. CADM1's reduced expression can be associated with a more aggressive phenotype and poorer patient outcomes. It is thought to play a role in ovarian cancer cell invasion and metastasis.
CADM1 and Breast Cancer
The role of CADM1 is context-dependent in breast cancer. In some cases, CADM1 has been found to be downregulated, and its loss has been associated with tumor progression and metastasis. In contrast, CADM1 has also been identified as a potential regulator of cell adhesion and epithelial-mesenchymal transition (EMT), suggesting a role in maintaining epithelial characteristics.
CADM1 and Head and Neck Squamous Cell Carcinoma (HNSCC)
CADM1 is often downregulated in HNSCC and may function as a tumor suppressor. Its reduced expression is correlated with more advanced tumor stages and a higher risk of metastasis.
CADM1 and Bladder Cancer
CADM1 is expressed in normal bladder epithelium and acts as a cell adhesion molecule, maintaining tissue integrity. In bladder cancer, CADM1 expression may be reduced, and its downregulation has been linked to tumor invasion and metastasis.
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