STKL1 Antibody

Introduction to STK11/LKB1 Antibodies

STK11 (serine/threonine kinase 11), also known as LKB1, is a tumor suppressor gene involved in energy metabolism, cell polarity, and immune regulation. Mutations in STK11/LKB1 are associated with cancer progression, particularly in non-small cell lung cancer (NSCLC) and resistance to PD-1/PD-L1 inhibitors . Antibodies targeting STK11/LKB1 are used to study its molecular mechanisms, validate its expression in tissues, and assess its prognostic significance in clinical settings.

Antibody Characteristics and Validation

STK11/LKB1 antibodies vary in specificity, clonality, and applications. Below are key findings from validated antibodies:

Critical Validation Strategies:

• Genetic Knockout Controls: Western blot (WB) and immunohistochemistry (IHC) experiments using KO cell lines (e.g., HEK293T LKB1/STK11 KO) confirm antibody specificity .

• Orthogonal Approaches: Comparing results with independent antibodies or protein knockdown techniques ensures reproducibility .

• Species Reactivity: Most antibodies target human STK11/LKB1, but cross-reactivity with other species (e.g., mouse) requires verification .

Western Blot (WB)

• Detection in Cancer Cells: AF8055 detects STK11/LKB1 in MCF-7 (breast cancer) and K562 (leukemia) cell lysates .

• Phosphorylation Status: Antibodies may be used to assess STK11/LKB1 activation (e.g., phosphorylated forms) in signaling pathways .

Immunohistochemistry (IHC)

• Tissue Localization: AF8055 highlights nuclear staining in breast cancer tissues, while cytoplasmic/nuclear staining is observed in normal breast tissue .

• Prognostic Biomarker: STK11/LKB1 expression levels correlate with tumor aggressiveness and immunotherapy response in NSCLC .

Clinical Relevance

Challenges and Considerations

1. Specificity and Cross-Reactivity:

   • Antibodies must be rigorously validated to avoid false positives, as seen in the "antibody characterization crisis" .

   • Example: AF8055’s specificity was confirmed using KO cell lines, eliminating non-specific bands .

2. Clinical Trial Context:

   • TNG260 + Pembrolizumab: Ongoing trials (e.g., NCT study) aim to restore immunotherapy efficacy in STK11-mutant tumors by targeting CoREST complexes .

   • PD-1 Blockade Resistance: STK11/LKB1 mutations correlate with reduced PD-L1 expression and neutrophil infiltration, limiting T-cell activity .

3. Technical Limitations:

   • Antibody Performance: Polyclonal antibodies (e.g., AF8055, 25471-1-AP) may lack the consistency of monoclonal alternatives .

   • Species Variability: Human-specific antibodies require retesting in preclinical models (e.g., murine Stk11/Lkb1 studies) .