Role And Mechanisms Of Cancer/testis Antigen CT45A1 To Promote Lung Cancer Cell Invasion And Metastasis

Cancer testis antigens(CTAs) were first defined by Vander Bruggen in 1991. Studies showed that CTAs were aberrantly overexpressed in various malignant tumors, including lung cancer, gastric cancer, liver cancer, colon cancer, breast cancer, prostate cancer, glioma, lymphoma and leukemia. CTAs can promote EMT and increase the tumorigenicity and are highly related to the prognosis of cancer patients. However, the mechanism of CTAs in tumor metastasis still needs to be further studied. Recently we reported that CT45A1 acted as an proto-oncogene to promote the growth, invasion and metastasis of breast cancer. More importantly, overexpression of CT45A1 is closely related to the tumor genesis, invasion and poor prognosis; whereas, the mechanism is still unknown.More recently, we found that CT45A1 was highly expressed in lung cancer. Lung cancer has high morbidity and malignancy and become a major threat to the health and life of human being. The five-year survival rate of lung cancer patients is only about 15%. The metastasis of lung cancer(especially brain and bone metastasis) is the main cause of death. The incidence of lung cancer and metastasis mechanism is still unclear. In the current study, we studied the role and mechanism of CT45A1 to promote invasion and metastasis of lung cancer cells. At first, we established the CT45A1 over-expressed NCI-H292 lung cancer cells and CT45A1 gene silenced 95 D lung cancer cells, respectively. Using these two models, we found that after highly expressed CT45A1 gene, the ability of invasion and metastasis of lung cancer cells significantly enhanced. On contrast, after silencing the CT45A1 gene,the invasion and metastasis ability of lung cancer cells decreased. Molecular biology study of CT45A1 in lung cancer cells revealed that CT45A1 promoted multiple cancer metastatic gene expression. Notably, CT45A1 can specificly bind to the promoter region of CXCR4, where located at-53 proximal to-72 bp, containing a transcription factor binding sites of SP1 consensus sequence cccgcccc. CT45A1 can also binds to another promoter region of CXCR4 at-1033 distal to-1052 bp, containing transcription factor NF-1binding sites of sequence gccaa. Coimmunoprecipitation results showed that CT45A1 can interact with NF-1 to form a complex. In additiona, we found that overexpression of CT45A1 in lung cancer cells constitutively activated transcript factor STAT3,suggesting that CT45A1 enhances lung cancer metastasis through escalating the transcription of the genes associated with cancer metastasis.In conclusion, CT45A1 CT45A1 serves as a transcriptional activator to promote transcription of key gene CXCR4, increase lung cancer cell migration and invasion, and enhance lung cancer metastasis. Our study revealed the role and mechanisms of CT45A1 in the invasion and metastasis of lung cancer cells, and may make contribution to elucidate the mechanism of lung cancer metastasis, and provide new thoughts and target for clinical lung cancer therapy.