The identification of tumor related membrane protein is important for both cancer diagnosis and targeted therapy. Currently, the number of ideal clinical biomarkers is still limited partially because of lacking efficient methods in biomarker discovery. Targeting peptides are generated by library screening and can recognize their cognate targets with high specificity and affinity. In addition, these functional peptides have been considered to be a valuable molecule for both imaging detection and targeting therapy in oncology. The selected peptides can be used to identify cell-surface protein biomarkers of cancer cells. In our study, the peptide (VECYLIRDNLCIY) derived from the bacteria displaying library worked as a bait to capture its binding partner and aldolase A was identified as the candidate. The results indicated that aldolase A' expression level on the cell membrane was regulated by PI3K and aldolase A located on the membrane could inhibit the aggression of tumors through mediating cell metabolic pathway. Aldolase A could work as the joint for the metabolic and signal pathways related to tumor progression. In our work, we demonstrated a promising technology for selecting and identifying binding partners for cell-specific peptides that enables discovery of new tumor biomarkers, showing great scientific study values and clinical translation potencies. SIGNIFICANCE: MS-based cancer biomarker discovery provides promising target candidates for cancer diagnosis and therapy. However, the inevitable limits make it inconvenient in the process of sample preparation and data analysis. In this way, the small molecular probes show some advantages due to their readily availability and specific binding affinity such as the aptamers screened with SELEX technology and peptides derived from displaying libraries. In the present study, aldolase A was proved to be the membrane binding partner of a specific peptidic ligand towards ZR-75-1 tumor cell. It was discovered that membrane aldolase A was more sensitive and observable than other subcellular fractions in response to cellular metabolic state alteration or glucose availability. In addition, the reduced membrane-localized aldolase A expression indicated a more aggressive tumor phenotype and was accompanied by the upregulation of MMP-2/MMP-9. The non-glycolysis activity endowed it with potential utility as a tumor diagnostic marker and therapeutic target. This work demonstrates the practicability of screened peptide in cancer biomarker discovery, facilitating the development of diagnostic tools and therapeutic approaches to cancer, and markedly improves our understanding of cancer biology.
Keywords: Aldolase a; Cell-surface capture，cancer biomarker; Peptide; Tumor aggressiveness.
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