1. TIM-4 promotes the growth of non-small-cell lung cancer in a RGD motif-dependent manner.
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Zhang, Qianqian, Wang, Hongxing, Wu, Xiaodong, Liu, Bing, Liu, Wen, Wang, Rong, Liang, Xiaohong, Ma, Chunhong, and Gao, Lifen
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IMMUNOGLOBULINS ,T cells ,MUCINS ,NON-small-cell lung carcinoma ,CANCER invasiveness ,GENE expression ,IMMUNOHISTOCHEMISTRY ,GENETICS ,ANALYSIS of variance ,ANIMAL experimentation ,BINDING sites ,CELL lines ,CELL physiology ,CHI-squared test ,GENES ,LUNG cancer ,LUNG tumors ,MEMBRANE proteins ,MICE ,MYOCARDIAL infarction ,PROBABILITY theory ,STATISTICS ,TUMOR markers ,DATA analysis software ,LOG-rank test - Abstract
Background: T-cell immunoglobulin domain and mucin domain 4 (TIM-4) is exclusively expressed in antigen-presenting cells and involved in immune regulation. However, the role of TIM-4 expressed in tumour cells remains completely unknown.Methods: Immunohistochemistry staining was used to examine TIM-4 or Ki-67 expression in tumour tissues. Real-time PCR or RT-PCR was performed to detect TIM-4 mRNA expression. Lung cancer cell growth and proliferation were conducted by CCK-8 assay and EdU staining. Cell cycle progression was analysed by flow cytometry. The PCNA and cell cycle-related proteins were verified by western blot. Co-IP assay was used to identify the interaction of TIM-4 and integrin αvβ3. The efficacy of TIM-4 in vivo was evaluated using xenograft tumour model.Results: The expression of TIM-4 in non-small-cell lung cancer (NSCLC) tissues was significantly higher than that of the adjacent tissues. Enhanced TIM-4 expression was negatively correlated with histological differentiation of lung carcinoma and lifespan of patients. Overexpression of TIM-4 promoted lung cancer cell growth and proliferation, and upregulated the expression of PCNA, cyclin A, cyclin B1 and cyclin D1, accompanied by accumulation of lung cancer cells in S phase. Interestingly, Arg-Gly-Asp (RGD) motif mutation abolished the effect of TIM-4 on lung cancer cells, which was further verified by tumour xenografts in mice. Furthermore, we found that TIM-4 interacted with αvβ3 integrin through RGD motif.Conclusions: This finding suggests that TIM-4 might be a potential biomarker for NSCLC that promotes lung cancer progression by RGD motif. [ABSTRACT FROM AUTHOR]- Published
- 2015
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