A number of previous studies have shown that the other members of the LIG family of proteins, such as Linx/Islr2, leucine-rich repeats and immunoglobulin-like domains-1 (Lrig1), adhesion molecule with immunoglobulin like domain 1 (Amigo1), and fibronectin leucine rich transmembrane 1 (Flrt1), interact with receptor tyrosine kinases (RTKs) to negatively or positively regulate their downstream signaling for neural development, differentiation control of tissue stem cells and cancer progression29, 43, 44, 45, 46 (Fig. 6A). This evidence concerns the gene ISLR2 and cancer.