Anti-DVL3 (aa 560-610) polyclonal antibody

Prostate cancer (PCa) was the fifth most common cancer overall in the world. More than 80% of patients died from PCa developed bone metastases. Caffeic acid phenethyl ester (CAPE) is a main bioactive component of honeybee hive propolis. Transwell and wound healing assays demonstrated that CAPE treatment suppressed the migration and invasion of PC-3 and DU-145 PCa cells. Gelatin zymography and Western blotting indicated that CAPE treatment reduced the abundance and activity of MMP-9 and MMP-2. Analysis using Micro-Western Array (MWA), a high-throughput antibody-based proteomics platform with 264 antibodies detecting signaling proteins involved in important pathways indicated that CAPE treatment induced receptor tyrosine kinase-like orphan receptor 2 (ROR2) in non-canonical Wnt signaling pathway but suppressed abundance of beta-catenin, NF-kappa B activity, PI3K-Akt signaling, and epithelial-mesenchymal transition (EMT). Overexpression or knockdown of ROR2 suppressed or enhanced cell migration of PC-3 cells, respectively. TCF-LEF promoter binding assay revealed that CAPE treatment reduced canonical Wnt signaling. Intraperitoneal injection of CAPE reduced the metastasis of PC-3 xenografts in tail vein injection nude mice model. Immunohistochemical staining demonstrated that CAPE treatment increased abundance of ROR2 and Wnt5a but decreased protein expression of Ki67, Frizzle 4, NF-kappa B p65, MMP-9, Snail, beta-catenin, and phosphorylation of I kappa B alpha. Clinical evidences suggested that genes affected by CAPE treatment (CTNNB1, RELA, FZD5, DVL3, MAPK9, SNAl1, ROR2, SMAD4, NFKBIA, DUSP6, and PLCB3) correlate with the aggressiveness of PCa. Our study suggested that CAPE may be a potential therapeutic agent for patients with advanced PCa.

Robinow syndrome (RS) is a well-recognized Mendelian disorder known to demonstrate both autosomal dominant and autosomal recessive inheritance. Typical manifestations include short stature, characteristic facies, and skeletal anomalies. Recessive inheritance has been associated with mutations in ROR2 while dominant inheritance has been observed for mutations in WNT5A, DVL1, and DVL3. Through trio whole genome sequencing, we identified a homozygous frameshifting single nucleotide deletion in WNT5A in a previously reported, deceased infant with a unique constellation of features comprising a 46,XY disorder of sex development with multiple congenital malformations including congenital diaphragmatic hernia, ambiguous genitalia, dysmorphic facies, shortened long bones, adactyly, and ventricular septal defect. The parents, who are both heterozygous for the deletion, appear clinically unaffected. In conjunction with published observations of Wnt5a double knockout mice, we provide evidence for the possibility of autosomal recessive inheritance in association with WNT5A loss-of-function mutations in RS.