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.
Highlights
Lung cancer is the leading cancer killer around the world [1], over 85% of lung cancers are diagnosed as non-small cell lung cancer (NSCLC)
According to the results from The Cancer Genome Atlas (TCGA), the expression levels of Annexin A5 (ANXA5) in NSCLC tissues were significantly lower in lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) (Table 1) compared to matched normal samples, which is consistent with our proteomic result from LUSC and adjacent normal tissues [6, 21]
Our early study had shown that there was no difference between NCI-H520 and pCDNA3.1-NCI-H520-NC cells (P
Summary
Lung cancer is the leading cancer killer around the world [1], over 85% of lung cancers are diagnosed as non-small cell lung cancer (NSCLC). Even though major progress in the understanding of cancer biology and treatment of lung cancer has been achieved over the last few years, the 1-year survival rate for NSCLC patients is still disappointing, which is below 15%[2]. More research is urgently needed to explore new mechanism-based modalities in oncogenesis and cancer progression. Quantitative Proteomic Profiling the Molecular Signatures of Annexin A5 in LSCC
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