Moreover, the same study shows that ovarian cancer sphere cells from cell lines and primary tumors maintain TIC-ness through an LPA autocrine loop, and that inhibition of ATX-LPA/AKT signaling prevents chemoresistance and tumorigenicity in these cells [55].The lysosphingolipid S1P is released from ceramides by ceramidases and phosphorylated by sphingosine kinase. This evidence concerns the gene ENPP2 and ovarian carcinoma.