Cancer/testis antigens trigger epithelial-mesenchymal transition and genesis of cancer stem-like cells

Abstract

Malignant tumors aberrantly overexpress various embryonic genes and proto-oncogenes, including a variety of cancer-testis antigens (CTAs). CTAs belong to a class of testis-derived proteins which are only expressed in germ cells in the male testis, and the expression of CTA genes is entirely silenced in the adult somatic tissues. They are, however, aberrantly overexpressed in a variety of malignant tumor tissues. Emerging evidence shows that a number of CTAs promote epithelialmesenchymal transition (EMT) and genesis of cancer stem like cells, escalating tumorigenesis, invasion, and metastasis. The can cer-testis antigens, such as SSX, MAGE-D4B, CAGE, piwil2, and CT45A1, upregulate EMT and metastatic genes, promoting EMT and tumor dissemination. In addition, certain members of CTAs, including Piwil2, DNAJB8, CT45A1, MAGE-A, GAGE, and SPANX, are implicated in the initiation or maintenance, of cancer stem-like cells, promoting tumorigenesis and malignant progression. Clinically CTAs are closely associated with poor prognosis in cancer patients. Intriguely, CTAs are strongly immunogenic and normally restricted to the male testis after birth, however, these proteins are aberrantly overexpressed in cancer stem-like cells and in a variety of cancers, suggesting their target potential for cancer immunotherapy, as diagnostic biomarkers, and as targets for novel anticancer drug discovery. Thus, the targeting of tumorigenic CTAs is a promising strategy to eradicate cancer stem-like cells and inhibit tumorigenesis for effective cancer treatment.