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Cancer/testis antigen (CTA)-45 family (CT45) belongs to a new family of genes in phylogenetics and is absent in normal tissues except for testis, but is aberrantly overexpressed in various cancer types. Whether CT45 and other CTAs act as proto-oncogenes has not been determined. Using breast cancer as a model, we found that CT45A1, a representative CT45 family member, alone had a weak tumorigenic effect. However, its neoplastic potency was greatly enhanced in the presence of growth factors. Overexpression of CT45A1 in breast cancer cells markedly upregulated various oncogenic and metastatic genes, constitutively activated ERK and CREB signaling pathways, promoted epithelial–mesenchymal transition, and increased cell stemness, tumorigenesis, invasion, and metastasis, whereas silencing CT45A1 significantly reduced cancer cell migration and invasion. We propose that CT45A1 functions as a novel proto-oncogene to trigger oncogenesis and metastasis. CT45A1 and other CT45 members are therefore excellent targets for anticancer drug discovery and targeted tumor therapy, and valuable genes in the study of a molecular phylogenetic tree.

The Neuronally expressed developmentally downregulated 4 (NEDD4), functioning largely as an E3 ubiquitin ligase, has been demonstrated to play a critical role in the development and progression of human cancers. In this review, to understand the regulatory mechanism(s) of NEDD4 as well as the signaling pathways controlled by NEDD4, we briefly describe the NEDD4 upstream regulators and its downstream ubiquitin substrates. Moreover, we further discuss its oncogenic roles in human malignancies. Therefore, targeting NEDD4 could be a potential therapeutic strategy for treatment of human cancers.

Summary Melanoma cells actively participate in tumor angiogenesis and vasculogenic mimicry. However, anti‐angiogenic therapy in patients with melanoma has not shown a significant survival gain. Thus, new anti‐melanoma angiogenic and vasculogenic drugs are highly desired. Using the metastatic melanoma cell line C8161 as a model, we explored melanoma vasculogenic inhibitors and found that lycorine hydrochloride (LH) effectively suppressed C8161 cell‐dominant formation of capillary‐like tubes in vitro and generation of tumor blood vessels in vivo with low toxicity. Mechanistic studies revealed that LH markedly hindered expression of VE‐cadherin in C8161 cells, but did not affect expression of six other important angiogenic and vasculogenic genes. Luciferase assays showed that LH significantly impeded promoter activity of the VE‐cadherin gene in a dose‐dependent manner. Together, these data suggest that LH inhibits melanoma C8161 cell‐dominant vasculogenic mimicry by reducing VE‐cadherin gene expression and diminishing cell surface exposure of the protein.