S100A10 Human

What is the molecular structure of human S100A10 and how does it differ from other S100 proteins?

Human S100A10 is a member of the S100 family of EF-hand calcium-binding proteins, but it stands unique among them. Unlike other S100 family members, S100A10 does not bind calcium despite having sequence and structural similarity to calcium-binding S100 proteins . The S100A10 monomer is an asymmetric protein composed of four alpha helices, and it can exist as a free monomer, a homodimer, or most commonly as a heterotetramer composed of a S100A10 dimer complexed with two molecules of annexin A2 . This heterotetramer can further dimerize through formation of two disulfide bonds.

The structural basis for S100A10's calcium-independence lies in mutations in its EF-hand domains that lock the protein in a permanently active conformation, mimicking the calcium-bound state of other S100 proteins. This constitutively active conformation allows S100A10 to interact with its binding partners without calcium regulation, which is a critical distinction from other S100 family members .

What are the standard methods for detecting S100A10 in human tissue samples?

Detection of S100A10 in human tissues can be accomplished through several established methods:

• Immunohistochemistry (IHC): As demonstrated in the kidney cancer tissue studies, S100A10 can be detected in paraffin-embedded tissue sections using specific antibodies such as Goat Anti-Human S100A10 Antigen Affinity-purified Polyclonal Antibody (AF1698). The protocol typically involves overnight incubation at 4°C followed by visualization with appropriate detection systems like HRP-DAB staining kits .

• Western blotting: For protein level quantification in tissue or cell lysates.

• RT-PCR and qPCR: For mRNA expression analysis.

• RNA-seq: For comprehensive transcriptomic profiling, as employed in hepatocellular carcinoma studies to identify differential expression patterns .

• Proteomics approaches: Including co-immunoprecipitation (Co-IP) experiments to identify protein-protein interactions, as demonstrated in studies examining S100A10's binding partners .

Optimal dilutions for antibodies should be determined by each laboratory for specific applications to ensure reliable and reproducible detection of S100A10 in different experimental contexts .

How is the S100A10 gene regulated at the transcriptional level?

S100A10 expression is regulated by a complex network of factors. The gene exhibits both constitutive expression in many cell types and inducible expression in response to numerous stimuli. Transcriptional regulation includes:

• Hormonal regulation: Dexamethasone has been shown to induce S100A10 expression .

• Growth factor signaling: Multiple growth factors upregulate S100A10, including epidermal growth factor (EGF), transforming growth factor-α (TGF-α), and nerve growth factor (NGF) .

• Cytokine signaling: Interferon-γ can induce S100A10 expression .

• Other physiological stimuli: Retinoic acid, thrombin, and keratinocyte growth factor have been demonstrated to upregulate S100A10 .

• Oncogenic regulation: The expression of oncogenes such as PML-RARα and KRas stimulates S100A10 levels, suggesting a role in oncogenesis .

This diverse regulation allows cells to modulate S100A10 levels in response to various physiological and pathological conditions, particularly in contexts requiring altered plasmin proteolytic activity .

What role does S100A10 play in cancer progression and metastasis?

S100A10 has emerged as a significant player in cancer biology, functioning through multiple mechanisms:

• Regulation of invasion and metastasis: S100A10 serves as a plasminogen receptor that mediates the production of plasmin, a broad-spectrum proteinase that degrades extracellular matrix components, facilitating cancer cell invasion and metastasis .

• Promotion of tumor growth: Overexpression of S100A10 in hepatocellular carcinoma (HCC) cells has been shown to increase proliferation and tumor size in vivo. In contrast, downregulation of S100A10 in HCC cell lines significantly reduces cell viability .

• Enhancement of migration and invasion: Experimental data demonstrates that S100A10 overexpression promotes HCC cell migration and invasion in vitro, while S100A10 knockdown inhibits these processes .

• Tumor microenvironment modulation: S100A10 regulates the recruitment of tumor-associated cells, particularly macrophages, to the tumor site, thereby influencing the tumor microenvironment .

• Immune evasion: Recent research has uncovered a novel role for S100A10 in CD8+ T cell exhaustion via the cPLA2 and 5-LOX axis, contributing to immune evasion in HCC. Silencing S100A10 inhibits CD8+ T cell exhaustion, potentially suppressing immune evasion mechanisms .

How does S100A10 contribute to the fibrinolytic system and what are the implications for thrombotic disorders?

S100A10 serves as a critical regulator of the fibrinolytic system through the following mechanisms:

• Plasminogen receptor function: S100A10 acts as a key cell surface receptor for plasminogen, significantly enhancing its conversion to the active protease plasmin. This process is essential for effective fibrinolysis—the dissolution of fibrin clots .

• Conservation of function: The plasminogen-binding site on S100A10 is highly conserved from mammals to fish, highlighting its evolutionary importance in regulating fibrinolysis .

• Contribution to total plasmin generation: S100A10 may account for as much as 50% of cellular plasmin generation, making it a major contributor to fibrinolytic activity .

• Colocalization of fibrinolytic components: S100A10 facilitates the colocalization of plasminogen with its activators, particularly tissue plasminogen activator (tPA), accelerating plasmin generation .

The S100A10-null mouse model has established the protein's critical role in fibrinolysis. Deficiencies in S100A10-dependent plasmin generation can lead to impaired fibrinolysis, potentially contributing to thrombotic disorders characterized by excessive fibrin deposition. Conversely, dysregulated S100A10 activity may contribute to pathological bleeding by enhancing fibrinolysis beyond normal physiological requirements .

Understanding S100A10's contribution to fibrinolysis may provide opportunities to develop targeted therapies for thrombotic disorders by modulating plasmin generation at the cellular level.

What evidence links S100A10 to mood disorders and depression?

The connection between S100A10 and mood disorders, particularly depression, is supported by several key findings:

• Neuronal expression and function: S100A10 is expressed in the brain of humans and other mammals, where it has been implicated in the regulation of mood through its interaction with neurotransmitter signaling systems .

• Serotonin signaling modulation: S100A10 interacts with serotonin-signaling proteins, a neurotransmitter system closely associated with mood regulation. Alterations in S100A10 levels correlate with symptoms of mood disorders .

• Therapeutic target potential: Due to its involvement in mood regulation, S100A10 represents a novel potential target for drug therapy in treating depression and other mood disorders .

• Expression changes in depression: Studies have observed altered S100A10 expression in the brains of individuals with depression, with reduced levels in specific brain regions associated with mood regulation.

• Animal models: In mouse models, S100A10 deficiency has been shown to produce depression-like behaviors, while antidepressant treatments can normalize or increase S100A10 expression.

These findings collectively suggest that S100A10 plays a significant role in the pathophysiology of mood disorders. The protein's involvement in neurotransmitter signaling, particularly serotonergic pathways, positions it as both a potential biomarker for mood disorders and a promising therapeutic target for novel antidepressant treatments .

How does the S100A10-Annexin A2 complex form and what functional significance does this have?

The S100A10-Annexin A2 complex formation and its functional significance involve several sophisticated molecular processes:

• Complex structure: S100A10 predominantly exists as part of a heterotetramer complex consisting of two S100A10 subunits bound to two annexin A2 molecules. This complex is referred to as the annexin A2 heterotetramer (AIIt) .

• Formation mechanism: The S100A10 homodimer binds to the N-terminal domains of annexin A2 molecules. This interaction is calcium-independent, unlike many other S100 protein interactions, as S100A10 exists in a permanently active conformation .

• Membrane localization: The complex localizes to the plasma membrane where annexin A2 anchors S100A10 to phospholipids. Without this association, free S100A10 is rapidly ubiquitinated and degraded by the proteasome, demonstrating the protective role of annexin A2 in stabilizing S100A10 .

• Functional significance:

  • Enhanced plasminogen activation: The complex significantly increases the efficiency of plasminogen activation on the cell surface by bringing together plasminogen and its activators .

  • Cell surface presentation: Annexin A2 is essential for the presentation of S100A10 on the cell surface, positioning it to function as a plasminogen receptor .

  • Signal transduction: The complex participates in various cellular signaling pathways.

  • Membrane trafficking: AIIt plays important roles in exocytosis and endocytosis by reorganizing F-actin .

  • Channel regulation: The complex regulates the function of various ion channels and receptors.

• Role in disease: The S100A10-Annexin A2 complex is implicated in various pathological conditions, including cancer, inflammation, and fibrinolysis disorders .

Understanding this complex formation provides insights into targeting S100A10-dependent processes while preserving other cellular functions that may rely on free S100A10 or annexin A2.

What is the role of S100A10 in immune regulation, particularly in the context of CD8+ T cell function?

Recent research has uncovered a significant role for S100A10 in immune regulation, with particular emphasis on CD8+ T cell function:

• CD8+ T cell exhaustion: S100A10 has been identified as a key mediator of CD8+ T cell exhaustion in the context of hepatocellular carcinoma (HCC). This exhaustion is characterized by T cells becoming functionally impaired and less effective at tumor elimination .

• Lipid metabolism pathway: S100A10 appears to regulate CD8+ T cell exhaustion via the cytosolic phospholipase A2 (cPLA2) and 5-lipoxygenase (5-LOX) axis, linking S100A10 to lipid metabolism reprogramming in the tumor microenvironment .

• Leukotriene B4 (LTB4) regulation: S100A10 activation of the cPLA2 and 5-LOX axis leads to upregulation of LTB4 levels, which promotes CD8+ T cell exhaustion in HCC tissues .

• Immune evasion mechanism: By inducing CD8+ T cell exhaustion, S100A10 facilitates immune evasion by HCC cells, ultimately impacting the growth and migration of HCC cells .

• Therapeutic implications: Silencing S100A10 has been shown to inhibit CD8+ T cell exhaustion, potentially suppressing immune evasion in HCC. This suggests that targeting S100A10 could enhance anti-tumor immunity by reinvigorating exhausted CD8+ T cells .

These findings represent a novel mechanistic link between S100A10, lipid metabolism, and immune regulation in the context of cancer. The S100A10-cPLA2-5-LOX axis provides potential therapeutic targets for enhancing anti-tumor immunity by preventing or reversing CD8+ T cell exhaustion .

What are the known binding partners of S100A10 beyond annexin A2 and what cellular processes do these interactions regulate?

S100A10 interacts with numerous proteins beyond annexin A2, participating in diverse cellular processes:

• Plasminogen and tPA: S100A10 directly binds plasminogen and tissue plasminogen activator, accelerating plasmin generation and regulating fibrinolysis and extracellular matrix remodeling .

• Membrane channels and receptors:

  • TASK-1 (K+ channel): S100A10 regulates the trafficking and function of this potassium channel.

  • TRPV5/6 (Ca2+ channels): S100A10 modulates the activity of these calcium channels.

  • 5-HT receptors: S100A10 interacts with serotonin receptors, influencing mood regulation and neurological function .

• Cytoskeletal components:

  • F-actin: S100A10 participates in reorganization of actin filaments, affecting cell morphology and movement .

  • Cytoskeletal regulatory proteins: S100A10 interacts with various proteins that regulate cytoskeletal dynamics.

• Enzymes:

  • Phospholipase A2 (cPLA2): S100A10 regulates this enzyme in the context of lipid metabolism and immune function .

  • 5-lipoxygenase (5-LOX): S100A10 activates this enzyme in lipid metabolism pathways, particularly in immune cells .

• Cell surface proteins:

  • AHNAK (Neuroblast differentiation-associated protein): Interacts with the S100A10-annexin A2 complex.

  • E-cadherin: S100A10 influences cell-cell adhesion through this interaction.

• Viral proteins: Several viruses exploit S100A10 for their life cycle, with viral proteins interacting directly with S100A10 to facilitate viral entry or assembly.

These diverse interactions position S100A10 at the intersection of multiple cellular processes, including membrane trafficking, signal transduction, cytoskeletal organization, and cell motility. The specific binding partners engaged by S100A10 likely vary depending on cell type and physiological context, providing a mechanism for cell-specific and context-dependent functions of this multifunctional protein .

What experimental models are most effective for studying S100A10 function in cancer research?

Various experimental models have proven effective for investigating S100A10 function in cancer research, each with specific advantages for addressing different research questions:

• Cell line models:

  • Overexpression systems: Cell lines such as Hep3B and Huh-7 with S100A10 overexpression have demonstrated increased proliferation, migration, and invasion capabilities .

  • Knockdown/knockout systems: SK-Hep-1 and HepG2 cells with S100A10 knockdown showed reduced cell viability, migration, and invasion .

  • Co-culture systems: Co-culture of CD8+ T cells with cancer cells (e.g., MHCC97-L) allows for investigation of S100A10's role in immune evasion and T cell exhaustion .

• Animal models:

  • Xenograft models: Injection of S100A10-overexpressing cancer cells (e.g., Hep3B) into immunocompromised mice has revealed larger tumor size compared to control cells, validating S100A10's role in tumor growth in vivo .

  • S100A10-null mice: These models have established S100A10's critical role as a regulator of fibrinolysis and oncogenesis .

  • HCC mouse models: Used to validate findings from cell culture experiments and investigate the role of S100A10 in tumor development in a physiologically relevant context .

• Patient-derived models:

  • Patient-derived xenografts (PDXs): These maintain tumor heterogeneity and microenvironment features.

  • Organoids: 3D cultures derived from patient tumors that can recapitulate aspects of the original tumor.

• Molecular and biochemical approaches:

  • Co-immunoprecipitation (Co-IP): Effective for identifying protein-protein interactions involving S100A10 .

  • RNA-seq analysis: Used to identify differentially expressed genes associated with S100A10 function .

  • Protein-protein interaction (PPI) analysis: Helps determine vital lipid metabolism genes and downstream factors associated with S100A10 .

• Clinical sample analysis:

  • Tissue microarrays: Allow for analysis of S100A10 expression across multiple patient samples.

  • Database analysis: Integration of data from GEO and TCGA databases has successfully identified S100A10 as a differentially expressed gene associated with lipid metabolism in HCC .

These diverse experimental approaches collectively provide a comprehensive toolkit for investigating S100A10's multifaceted roles in cancer biology, from molecular mechanisms to clinical relevance.

What are the most recent technological advances in targeting S100A10 for potential therapeutic applications?

Recent technological advances in targeting S100A10 for therapeutic applications span several innovative approaches:

• RNA interference (RNAi) and gene silencing technologies:

  • Small interfering RNAs (siRNAs) targeting S100A10 have shown efficacy in reducing cancer cell proliferation, migration, and invasion in preclinical models .

  • Short hairpin RNA (shRNA) approaches for stable knockdown of S100A10 have demonstrated potential in suppressing tumor growth .

• CRISPR-Cas9 gene editing:

  • Precise deletion or mutation of S100A10 using CRISPR-Cas9 technology allows for detailed functional studies and potential therapeutic applications.

  • Knock-in models can be used to study specific domains or mutations of S100A10.

• Therapeutic antibodies and peptides:

  • Antibodies targeting the S100A10-annexin A2 complex or specific functional domains of S100A10 are being explored.

  • Peptide mimetics designed to interfere with S100A10 interactions with specific binding partners offer targeted approach to inhibiting select functions while preserving others.

• Small molecule inhibitors:

  • Structure-based drug design targeting the interface between S100A10 and its binding partners is an active area of research.

  • High-throughput screening has identified compounds that can disrupt specific S100A10 protein-protein interactions.

• Targeted drug delivery systems:

  • Nanoparticle-based delivery of S100A10 inhibitors to tumor sites improves efficacy while reducing systemic side effects.

  • Conjugation of S100A10 targeting agents with cytotoxic drugs creates targeted cancer therapeutics.

• Immune-based approaches:

  • Targeting the S100A10-cPLA2-5-LOX axis to prevent CD8+ T cell exhaustion represents a novel immunotherapeutic strategy in cancer .

  • Combination therapies linking S100A10 inhibition with immune checkpoint inhibitors may enhance anti-tumor immune responses.

These technological advances provide multiple avenues for therapeutic targeting of S100A10 in various disease contexts, particularly in cancer where S100A10 has been established as a novel oncogene promoting proliferation, invasion, and migration . The ability to target specific functions or interactions of S100A10 offers the potential for precision medicine approaches tailored to individual patient needs.

What are the optimal techniques for studying S100A10-protein interactions and identifying new binding partners?

Several sophisticated techniques are available for studying S100A10-protein interactions and discovering novel binding partners:

• Co-immunoprecipitation (Co-IP):

  • Classical method for confirming protein-protein interactions in native conditions.

  • Can be coupled with mass spectrometry (IP-MS) for unbiased identification of binding partners.

  • Has been successfully employed in studies examining S100A10's interactions, particularly in the context of lipid metabolism and immune function .

• Proximity-based labeling techniques:

  • BioID: Fusion of S100A10 with a biotin ligase to biotinylate proximal proteins.

  • APEX: Uses an engineered peroxidase for proximity labeling.

  • These methods capture both stable and transient interactions in living cells.

• Yeast two-hybrid (Y2H) screening:

  • Allows for high-throughput screening of protein-protein interactions.

  • Can identify direct binary interactions between S100A10 and potential partners.

• Protein microarrays:

  • Enables screening of interactions between purified S100A10 and thousands of proteins simultaneously.

  • Useful for identifying direct interactions in a controlled environment.

• Surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC):

  • Provide quantitative measurements of binding affinities and kinetics.

  • Essential for characterizing the strength and dynamics of S100A10 interactions.

• Structural biology approaches:

  • X-ray crystallography: Determines atomic-level structures of S100A10-protein complexes.

  • Cryo-electron microscopy (cryo-EM): Particularly useful for larger complexes like the S100A10-annexin A2 heterotetramer.

  • NMR spectroscopy: Provides information about dynamic interactions and flexible regions.

• Computational approaches:

  • Protein-protein interaction (PPI) prediction algorithms: Used to identify potential binding partners based on sequence or structural features .

  • Molecular docking: Simulates the interaction between S100A10 and candidate binding partners.

• Fluorescence-based techniques:

  • Förster resonance energy transfer (FRET): Detects protein interactions in living cells.

  • Fluorescence correlation spectroscopy (FCS): Measures diffusion properties that change upon complex formation.

  • Bimolecular fluorescence complementation (BiFC): Visualizes protein interactions in cellular contexts.

These methodologies can be employed in complementary ways to provide comprehensive characterization of S100A10 interactions, from initial discovery to detailed mechanistic understanding. The combination of unbiased screening approaches with targeted validation and quantitative characterization represents the optimal strategy for studying S100A10's diverse interactome .

What are the major contradictions or knowledge gaps in our understanding of S100A10 function?

Despite significant advances in S100A10 research, several contradictions and knowledge gaps persist:

• Tissue-specific functions:

  • While S100A10's role has been well-characterized in certain tissues and cancers (such as HCC), its function in other tissue contexts remains poorly understood.

  • The apparent contradictory roles of S100A10 across different tissue types suggest context-dependent functions that require further elucidation.

• Calcium-independent mechanism:

  • Despite being a member of the S100 family of calcium-binding proteins, S100A10 does not bind calcium . The evolutionary advantage of this calcium-independence and how it influences S100A10's functional repertoire compared to calcium-binding S100 proteins requires further investigation.

• Subcellular localization dynamics:

  • The mechanisms governing S100A10's distribution between intracellular compartments and the cell surface remain incompletely understood.

  • How cells regulate the proportion of S100A10 engaged in different functions (e.g., plasminogen receptor vs. channel regulation) is unclear.

• Immune regulatory role:

  • The recently discovered role of S100A10 in CD8+ T cell exhaustion represents a novel function , but how this intersects with its other known functions remains to be determined.

  • Whether S100A10's immune regulatory functions extend beyond CD8+ T cells to other immune cell types is unknown.

• Therapeutic targeting challenges:

  • Given S100A10's involvement in multiple physiological processes, selective targeting of its pathological functions while preserving normal functions presents a significant challenge.

  • The potential for compensatory mechanisms when S100A10 is inhibited has not been thoroughly explored.

• Signaling pathway integration:

  • How S100A10 integrates signals from multiple pathways and binding partners to coordinate cellular responses remains poorly understood.

  • The hierarchy of S100A10's interactions with different binding partners under various physiological conditions needs clarification.

• Post-translational modifications:

  • The extent and significance of post-translational modifications of S100A10 beyond its interaction with annexin A2 are not well characterized.

• Biomarker potential:

  • While S100A10 overexpression correlates with poor outcomes in certain cancers , its utility as a diagnostic or prognostic biomarker across different disease contexts requires validation.

Addressing these knowledge gaps will require integrative approaches combining advanced molecular techniques, diverse experimental models, and clinical correlations to build a more comprehensive understanding of S100A10's multifaceted biology.

How can researchers effectively design experiments to distinguish S100A10-specific effects from those mediated by the annexin A2 complex?

Designing experiments to differentiate S100A10-specific effects from those mediated by the annexin A2 complex requires sophisticated methodological approaches:

• Domain-specific mutations and truncations:

  • Generate S100A10 mutants that cannot bind annexin A2 while preserving other functions.

  • Create annexin A2 variants unable to bind S100A10 but retaining other functional domains.

  • Compare phenotypes of cells expressing these mutants to identify specific contributions of each protein and their complex.

• Selective silencing and rescue experiments:

  • Knockdown/knockout S100A10 and rescue with either wild-type S100A10 or annexin A2-binding deficient mutants.

  • Similarly, knockdown annexin A2 and rescue with wild-type or S100A10-binding deficient mutants.

  • These complementary approaches can reveal functions dependent on the complex versus individual proteins.

• Competitive inhibition strategies:

  • Use peptides or small molecules that specifically disrupt the S100A10-annexin A2 interaction without affecting other functions.

  • Apply these tools in functional assays to determine which processes require the intact complex.

• Subcellular targeting approaches:

  • Create fusion proteins that direct S100A10 to specific subcellular locations independent of annexin A2.

  • Assess whether S100A10 retains functionality when localized to these alternative sites.

• Temporal regulation systems:

  • Implement inducible expression systems for S100A10 and annexin A2 with different induction kinetics.

  • Analyze time-dependent phenotypes to separate immediate (likely direct) effects from delayed (likely indirect) effects.

• Binding partner-specific assays:

  • Design assays that specifically measure interaction with known S100A10-specific binding partners (like plasminogen) versus complex-specific binding partners.

  • Compare these interactions in the presence and absence of functional annexin A2.

• Proteomics approaches:

  • Perform differential interactome analysis comparing S100A10 alone versus the S100A10-annexin A2 complex.

  • Identify proteins that interact exclusively with S100A10 or exclusively with the complex.

• Single-molecule imaging techniques:

  • Track the dynamics of fluorescently labeled S100A10 and annexin A2 to identify locations and contexts where they function independently versus as a complex.

These methodological approaches, used in combination, can effectively disentangle the specific functions of S100A10 from those requiring the annexin A2 complex, leading to a more nuanced understanding of S100A10 biology and potential therapeutic targeting strategies.

What are the promising future directions for S100A10 research in relation to personalized medicine approaches?

The field of S100A10 research offers several promising avenues for personalized medicine approaches:

• Biomarker development for stratification:

  • S100A10 expression patterns could serve as biomarkers for patient stratification in cancers such as HCC, where its overexpression correlates with poor survival outcomes .

  • Multi-parameter profiling combining S100A10 with other markers may enhance predictive accuracy for treatment response or disease progression.

• Precision targeting based on molecular profiles:

  • Development of therapies targeting specific S100A10 interactions or functions relevant to individual patient disease profiles.

  • Identifying patient subgroups whose tumors are particularly dependent on S100A10-mediated processes for growth or metastasis.

• Combination therapy approaches:

  • Integration of S100A10 targeting with other therapeutic modalities based on comprehensive molecular profiling.

  • For instance, combining S100A10 inhibition with immune checkpoint inhibitors in patients with evidence of S100A10-mediated CD8+ T cell exhaustion .

• Monitoring treatment response:

  • Using S100A10 levels or activity as biomarkers for monitoring response to therapies that directly or indirectly affect S100A10-dependent pathways.

  • Development of liquid biopsy approaches to detect circulating markers of S100A10 activity.

• Novel therapeutic targets within S100A10 pathways:

  • The S100A10-cPLA2-5-LOX axis represents a promising target for preventing CD8+ T cell exhaustion in cancer .

  • Identification of patient-specific downstream effectors of S100A10 that could be targeted in a personalized manner.

• Biomarker-guided clinical trials:

  • Design of clinical trials that select patients based on S100A10 expression or activity levels.

  • Implementation of adaptive trial designs that adjust treatment based on changes in S100A10-related biomarkers.

• Pharmacogenomic approaches:

  • Identification of genetic variants that influence S100A10 expression, function, or response to targeted therapies.

  • Development of companion diagnostics to guide selection of patients for S100A10-targeted therapies.

• Integration with multi-omics data:

  • Combining S100A10 expression data with genomic, transcriptomic, proteomic, and metabolomic profiles to develop comprehensive disease signatures.

  • Application of machine learning algorithms to identify complex patterns associated with S100A10 dysregulation and therapeutic vulnerabilities.

These future directions highlight the potential of S100A10 research to contribute significantly to personalized medicine approaches, particularly in oncology but potentially extending to other disease areas where S100A10 plays significant roles, such as thrombotic disorders and mood regulation .