ANXA8 shares the conserved structural features of annexins: a variable N-terminal domain and a C-terminal core containing four calcium-binding repeats . Key features include:
Binding Affinity: Interacts with Ca²⁺ ions and phospholipids, modulating membrane dynamics .
Subcellular Localization: Primarily cytoplasmic, with membrane-associated activity in specific contexts .
Variable | Low ANXA8 (n=63) | High ANXA8 (n=89) | p-value |
---|---|---|---|
TNM Stage (III/IV) | 35 | 70 | 0.002 |
Poor Differentiation | 18 | 69 | <0.001 |
Lymph Node Metastasis | 37 | 62 | 0.111 |
Data sourced from |
Biomarker Potential: Upregulated in RCC, with higher expression linked to advanced histological grades and poor OS .
Functional Impact: May regulate cell cycle progression, though mechanisms remain under investigation .
Subpopulation Marker: Expressed in quiescent c-Kit⁺/ERα⁻ luminal progenitors, associated with basal-like subtypes .
Cell Cycle Regulation: Overexpression induces G₀/G₁ arrest in mammary epithelial cells .
ANXA8’s prognostic utility spans multiple cancers:
GC: Independent predictor of OS (HR = 2.293, 95% CI: 1.317–3.991) and DFS .
RCC: High expression correlates with reduced survival (HR = 2.31) .
Atherosclerosis: Germline Anxa8 deficiency delays plaque progression in murine models, suggesting endothelial ANXA8 inhibition as a therapeutic strategy .
Cancer Therapy: Potential for targeting ANXA8 in GC and RCC, though clinical validation is pending .
Blood Coagulation: Acts as an anticoagulant by inhibiting thromboplastin-specific complexes .
Mammary Gland Development: Expressed in quiescent epithelial cells during puberty and involution .
Mechanistic Gaps: Limited understanding of ANXA8’s role in non-cancerous conditions, such as metabolic regulation.
Diagnostic Potential: Needs validation as a prognostic marker in larger cohorts.
Therapeutic Exploitation: Further studies required to explore ANXA8 inhibition in atherosclerosis and cancer.
Q: How can I design an experiment to study the expression of Annexin A8 in human tissues? A: To study ANXA8 expression, you can use techniques like Western blotting and immunohistochemistry (IHC). For Western blotting, use a specific antibody (e.g., Sheep Anti-Human Annexin A8 Antigen Affinity-purified Polyclonal Antibody) and optimize the dilution for your samples . For IHC, perform heat-induced epitope retrieval and use a staining kit to visualize ANXA8 in tissue sections .
Q: How can I analyze genes co-expressed with ANXA8 to understand its biological functions? A: Use databases like cBioPortal to identify co-expressed genes with a Spearman’s correlation coefficient > 0.30. Then, apply functional and pathway enrichment analysis using tools like DAVID to understand the biological pathways involved .
Q: How do I address contradictions in research findings regarding the role of ANXA8 in different diseases? A: Analyze the experimental designs, sample sizes, and statistical methods used in conflicting studies. Consider factors like tissue specificity and disease context. For instance, ANXA8 may have different roles in atherosclerosis versus leukemia .
Q: What factors should I consider when selecting an antibody for ANXA8 detection? A: Choose antibodies based on specificity, sensitivity, and compatibility with your experimental method. For example, use affinity-purified polyclonal antibodies for Western blotting and IHC .
Q: How can I use advanced techniques like RT-PCR to study ANXA8 expression in specific cell types? A: Use RT-PCR with specific primers (e.g., Hs04190981 for human ANXA8) to quantify ANXA8 mRNA levels in cell lysates. Normalize expression to housekeeping genes like GAPDH or 18S rRNA .
Q: How does ANXA8 regulate the Wnt signaling pathway? A: ANXA8 acts as a regulator of Wnt signaling, influencing cellular phenotypes. Investigate this interaction by analyzing the effects of ANXA8 overexpression or knockdown on Wnt pathway components .
Q: What role does ANXA8 play in atherosclerosis progression? A: ANXA8 is upregulated in atherosclerotic plaques and contributes to disease progression. Study its role by analyzing plaque formation and inflammation markers in ANXA8-deficient models .
Q: How does ANXA8 interact with the immune system? A: ANXA8 influences leukocyte recruitment by modulating cell surface markers like CD63. Investigate this interaction using endothelial cell models and flow cytometry .
Q: How can I analyze the structural features of ANXA8? A: Use resources like the Human Protein Atlas to visualize ANXA8's structure and predicted isoforms. Analyze transmembrane regions and antigen sequences for antibody binding .
Q: Can ANXA8 serve as a prognostic biomarker for diseases? A: Yes, ANXA8 has potential as a biomarker due to its association with disease progression. Evaluate its prognostic value by analyzing expression levels in patient samples and correlating them with clinical outcomes .
Tissue Type | ANXA8 Expression Level |
---|---|
Placenta | High |
Atherosclerotic Plaques | Elevated |
Lung Carcinoma Cells | Variable |
Annexin A8 (ANXA8) is a member of the annexin family, which consists of calcium-dependent membrane and phospholipid-binding proteins. These proteins are involved in various cellular processes, including membrane trafficking, inflammation, and apoptosis. Annexin A8, like other annexins, contains four annexin repeats separated by linking sequences of variable lengths .
The annexin family was first discovered in 1977 with the identification of synexin (now known as annexin A7), which caused the aggregation of chromaffin granules in the adrenal glands in the presence of free calcium . Annexin A8 shares structural similarities with other annexins, featuring a conserved core domain that binds calcium and phospholipids, and a variable N-terminal region that may confer specific functions .
Annexin A8 plays a crucial role in various cellular processes:
Recombinant human annexin A8 is produced using recombinant DNA technology, which involves inserting the gene encoding annexin A8 into a suitable expression system, such as bacteria or mammalian cells. This allows for the large-scale production of the protein for research and therapeutic purposes.
Annexin A8, along with other annexins, has shown potential in various therapeutic applications. Studies have demonstrated positive outcomes in animal models of sepsis, myocardial infarction, and ischemia-reperfusion injury when treated with recombinant human annexins and annexin analogue peptides . These findings suggest that annexin A8 could be a valuable therapeutic agent in the treatment of inflammatory and ischemic conditions.