No abstract

No abstract

No abstract

No abstract

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.

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.

Aggressive cancer cells gain robust tumor vascular mimicry (VM) capability that promotes tumor growth and metastasis. is aberrantly overexpressed in vasculogenic cancer cells and regarded as a master gene of tumor VM. Although microRNAs (miRNAs) play an important role in modulating tumor angiogenesis and cancer metastasis, the miRNA that targets expression in cancer cells to inhibit tumor cell-mediated VM is enigmatic. In this study, we found that miR-27b levels are negatively co-related to expression in ovarian cancer cells and tumor cell-mediated VM, and demonstrated that miR-27b could bind to the 3'-untranslated region (3'UTR) of mRNA. Overexpression of miR-27b in aggressive ovarian cancer cell lines Hey1B and ES2 significantly diminished intracellular expression; convincingly, the inhibitory effect of miR-27b could be reversed by miR-27b specific inhibitor. Intriguingly, miR-27b not only effectively suppressed ovarian cancer cell migration and invasion, but also markedly inhibited formation of ovarian cancer cell-mediated capillary-like structures in vitro and suppressed generation of functional tumor blood vessels in mice. Together, our study suggests that miR-27b functions as a new inhibitor of ovarian cancer cell-mediated VM through suppression of expression, providing a new potential drug candidate for antitumor VM and anti-ovarian cancer therapy.

No abstract