Fringe family genes and their modulation of Notch signaling in cancer

Fringes are glycosyltransferases that transfer N-acetylglucosamine to the O-linked fucose of Notch receptors. They regulate the Notch signaling activity that drives tumor formation and progression, resulting in poor prognosis. However, the specific tumor-promoting role of Fringes differs depending on the type of cancer. Although a particular Fringe member could act as a tumor suppressor in one cancer type, it may act as an oncogene in another. This review discusses the tumorigenic role of the Fringe family (lunatic fringe, manic fringe, and radical fringe) in modulating Notch signaling in various cancers. Although the crucial functions of Fringes continue to emerge as more mechanistic studies are being pursued, further translational research is needed to explore their roles and therapeutic benefits in various malignancies.