Folates are B vitamins that function in one-carbon metabolism. Folate receptors are one of three major types of folate transporters. The folate receptors FOLR1 and FOLR2 are overexpressed in multiple cancers. The overexpression of FOLR1 is often associated with increased cancer progression and poor patient prognosis. There is emerging evidence that FOLR1 is involved in signaling pathways that are independent of one-carbon metabolism. Recent publications implicate a direct role of FOLR1 in three signaling pathways: JAK–STAT3, ERK1/2, and as a transcription factor. Six other signaling pathways have been proposed to include FOLR1, but these currently lack sufficient data to infer a direct signaling role for FOLR1. We discuss the data that support noncanonical roles for FOLR1, and its limitations.

叶酸是在单碳代谢中起作用的 B 族维生素。叶酸受体是叶酸转运蛋白的三种主要类型之一。叶酸受体 FOLR1 和 FOLR2 在多种癌症中过度表达。FOLR1 的过度表达通常与癌症进展加快和患者预后不良有关。越来越多的证据表明 FOLR1 参与了独立于单碳代谢的信号通路。最近的出版物暗示了 FOLR1 在三个信号通路中的直接作用：JAK–STAT3、ERK1/2 和作为转录因子。已提议包括 FOLR1 在内的其他六种信号通路，但这些目前缺乏足够的数据来推断 FOLR1 的直接信号作用。我们讨论了支持 FOLR1 非规范角色的数据及其局限性。