Emerging roles for folate receptor FOLR1 in signaling and cancer

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.