2.2.6 Hippo-Yes-associated protein (YAP)
Xiangxiang Zhou et al 47 determined that YAP expression was up-regulated in DLBCL, and its excessive expression could appreciably increase the growth, invasion and angiogenesis capacity of DLBCL cells. YAP is overexpressed in a variety of cancers and is associated with disease progression. Knockdown YAP by shRNA or CRISPR/Cas9 induced cell cycle arrest and promoted the expression of downstream YAP target genes CTGF and CYR61. The benzoporphyrin derivative Verteporfin (VP) induced a dose-dependent reduction in the expression levels of YAP and TEAD, while inhibiting the expression of the YAP downstream target genes CTGF and CYR61, thus exerting anti-tumor effects. IGF-1R is a tyrosine kinase, inhibition IGF-1R resulting in reduced expression of YAP and its downstream molecules. Supplementation of IGF-1 can reverse IGF-1R decrease the YAP protein level caused by downregulation. To determine how the loss of IGF-1R affects Hippo-Yap signals in DLBCL, PPP or AG1024, a member of the tyrosine molecular class and a cyclic ligand alkaloid, were added to DLBCL cells, both of which inhibit IGF1R activity. Increased expression of MST1(a key protein in Hippo-Yap signaling) was observed after addition. This confirms that IGF-1R may be an upstream regulator of Hippo-Yap signaling pathway, and its depletion can enhance Hippo-Yap signaling pathway.