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.