FZD2, FZD5 and ROR2 are internalized in a WNT5A and clathrin-dependent manner

Stimulation of HEK293, HeLaS3 or KKLS gastric cancer cells with WNT5A promotes the internalization of FZD2, FZD5 and ROR2. Internalization is required for RAC activation downstream of WNT5A and subsequent activation of laminin gamma 2 gene expression which is associated with metastasis and invasion in gastric cancer (Sato et al, 2010; Hanaki et al, 2012; Yamamoto et al, 2009). Knockdown or inhibition of clathrin abrogates receptor internalization and RAC activation suggesting that clathrin-mediated endocytosis is required for this WNT5A-dependent signaling (Sato et al, 2010; Hanaki et al, 2012).

WNT5A对HEK293、HeLaS3或KKLS胃癌细胞的刺激，可促进FZD2、FZD5和ROR2的内吞作用。内吞作用是WNT5A下游RAC激活及随后的层粘连蛋白γ2基因表达激活的必要条件，而层粘连蛋白γ2基因表达与胃癌的转移和侵袭相关（Sato等，2010；Hanaki等，2012；Yamamoto等，2009）。敲低或抑制网格蛋白可消除受体内吞和RAC激活，这表明网格蛋白介导的内吞作用对于此WNT5A依赖性信号传导是必需的（Sato等，2010；Hanaki等，2012）。