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Neuron-derived neurotrophic factor (NDNF) is a glycosylated, disulfide-bonded secretory protein that contains a fibronectin type III domain. NDNF has been identified as a neurotrophic factor; however, its role in carcinogenesis has not yet been identified. To investigate the expression and role of NDNF in carcinogenesis, the expression of NDNF in human Renal cell carcinoma (RCC) cell lines and tissues was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Cell proliferation was investigated using CCK-8 and colony formation assays, and the cell invasion and immigration capacity was evaluated using the transwell assay. The results demonstrated that NDNF expression was downregulated in RCC cell lines and RCC tissues. Restoring NDNF expression significantly inhibited the proliferation, migration and invasion of RCC cells. The study also demonstrated that the inhibitory effect of NDNF on invasive ability was mediated by suppressing the epithelial-mesenchymal transition (EMT) in RCC cells. NDNF may therefore be considered an important regulator of EMT in RCC progression and may represent a novel promising target for antimetastatic therapy. [ABSTRACT FROM AUTHOR]

Human CMTM3 has been proposed as a putative tumor suppressor gene. The loss of CMTM3 has been found in several carcinomas. However, the regulation of CMTM3 expression and its function in tumor progression remain largely unknown. Here, we investigated the regulation of CMTM3 expression, function and molecular mechanism in human testicular cancer cells. CMTM3 was frequently downregulated or silenced in testicular cancer cell lines and tumor tissues but highly expressed in normal testis tissues. The re-expression of CMTM3 significantly suppressed the colony formation, proliferation, and migration capacity of testicular cancer cells by inducing a G2 cell cycle arrest and apoptosis. Moreover, the re-expression of CMTM3 activated the transcription of p53, induced p53 accumulation, up-regulated the expression of p21, and increased the cleavage of caspase 9, 8, 3, and PARP. The downregulation of CMTM3 in clinical tumor tissues was associated with the methylation of a single CpG site located within the Sp1/Sp3-responsive region of the core promoter. These results indicate that CMTM3 can function as tumor suppressor through the induction of a G2 cell cycle arrest and apoptosis. CMTM3 is thus involved in testicular cancer pathogenesis, and it is frequently at least partially silenced by the methylation of a single, specific CpG site in tumor tissues. [ABSTRACT FROM AUTHOR]