Background: T-cell immunoglobulin and mucin domain 1 (TIM-1) is an important co-stimulatory molecule which serves as a surface marker for T cell activation, especially for Th2 cells. Recently, many studies have also shown that TIM-1 can be abnormally expressed in human cancers and may have a potential role in promoting cancer progression.
Methods: The immunohistochemistry was used to examine the TIM-1 expression in human non-small-cell lung carcinoma (NSCLC) tissues. The cellular studies were performed to investigate the role of TIM-1 in the regulation of biological functions of human lung cancer cell lines.
Results: We found that the TIM-1 expression was increased in human NSCLC tissues compared with the adjacent normal tissues, and the OS rate of NSCLC patients with higher TIM-1 expression was significantly lower compared with the ones with lower TIM-1 expression. The COX model showed that higher TIM-1 expression in lung cancer tissues could be used as an independent prognostic predictor for the patients. Furthermore, we depleted TIM-1 in NSCLC cell lines A549 and SK-MES-1, and the cellular functional studies also revealed that depletion of TIM-1 could significantly inhibit the cell viability as well as the abilities of migration and invasion. In addition, our microarray data showed that certain signaling pathways were altered and enriched after depletion of TIM-1. We subsequently verified that PI3K/Akt signaling pathway was involved in the TIM-1-mediated regulation of cellular functions in NSCLC cells.
Conclusion: Our findings supported the notion that TIM-1 could serve as a potential therapeutic target for NSCLC.
Keywords: Immunohistochemistry; Lung cancer; Prognosis; RNAi; TIM-1.