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Quantitative Mass Spectrometric Profiling of Cancer-cell Proteomes Derived From Liquid and Solid Tumors
Published on: February 27, 2015
Quantitative Proteomic Profiling the Molecular Signatures of Annexin A5 in Lung Squamous Carcinoma Cells
Bing Sun1,2, Yuxin Bai2, Liyuan Zhang2
1Department of Thoracic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, Liaoning, China.
Abstract:
Lung cancer remains the leading cancer killer around the world. It's crucial to identify newer mechanism-based targets to effectively manage lung cancer. Annexin A5 (ANXA5) is a protein kinase C inhibitory protein and calcium dependent phospholipid-binding protein, which may act as an endogenous regulator of various pathophysiological processes. However, its molecular mechanism in lung cancer remains poorly understood. This study was designed to determine the mechanism of ANXA5 in lung cancer with a hope to obtain useful information to provide a new therapeutic target. We used a stable isotope dimethyl labeling based quantitative proteomic method to identify differentially expressed proteins in NSCLC cell lines after ANXA5 transfection. Out of 314 proteins, we identified 26 and 44 proteins that were down- and up-regulated upon ANXA5 modulation, respectively. The IPA analysis revealed that glycolysis and gluconeogenesis were the predominant pathways modulated by ANXA5. Multiple central nodes, namely HSPA5, FN1, PDIA6, ENO1, ALDOA, JUP and KRT6A appeared to occupy regulatory nodes in the protein-protein networks upon ANXA5 modulation. Taken together, ANXA5 appears to have pleotropic effects, as it modulates multiple key signaling pathways, supporting the potential usefulness of ANXA5 as a potential target in lung cancer. This study might provide a new insight into the mechanism of ANXA5 in lung cancer.
Insights
Annexin A5 (ANXA5) shows potential as a novel lung cancer target by modulating key signaling pathways, including glycolysis. This study identified specific protein changes and regulatory nodes, offering new therapeutic insights for non-small cell lung cancer (NSCLC).
Area of Science:
- Molecular Oncology
- Cancer Biology
- Proteomics
Background:
- Lung cancer is a leading global cause of cancer mortality.
- Novel, mechanism-based therapeutic targets are essential for effective lung cancer management.
- The molecular role of Annexin A5 (ANXA5) in lung cancer pathogenesis is largely uncharacterized.
Purpose of the Study:
- To elucidate the molecular mechanism of ANXA5 in lung cancer.
- To identify potential therapeutic targets for lung cancer based on ANXA5 function.
- To investigate the impact of ANXA5 modulation on protein expression and signaling pathways in non-small cell lung cancer (NSCLC) cells.
Main Methods:
- Stable isotope dimethyl labeling-based quantitative proteomics was employed to identify differentially expressed proteins.
- ANXA5 was transfected into NSCLC cell lines to study its effects.
- Ingenuity Pathway Analysis (IPA) was used to analyze modulated pathways and protein-protein interaction networks.
Main Results:
- ANXA5 modulation resulted in the differential expression of 26 down-regulated and 44 up-regulated proteins out of 314 identified proteins.
- IPA revealed that glycolysis and gluconeogenesis were significantly modulated by ANXA5.
- Key regulatory nodes in protein-protein networks, including HSPA5, FN1, PDIA6, ENO1, ALDOA, JUP, and KRT6A, were identified.
Conclusions:
- ANXA5 exhibits pleiotropic effects, modulating multiple critical signaling pathways in lung cancer.
- These findings support the potential of ANXA5 as a novel therapeutic target for lung cancer.
- The study provides new insights into the molecular mechanisms underlying ANXA5's role in lung cancer.
