KDELR1 and Cowden syndrome 1: Furthermore, we showed that KDELR1 knockdown and consequent inhibition of the malignant behaviors of CS, is achieved by promoting the expression of MAP4K4 via ITG-α3/5β5-PLCγ followed by YAP1 accumulation in cytoplasm and its inactivation, and subsequent Hippo-YAP1 signaling pathway.