神经细胞黏附分子通过非Wnt依赖的β-catenin途径促进小鼠黑色素瘤细胞增殖

 目的：研究神经细胞黏附分子（neural cell adhesion molecule, NCAM）对小鼠黑色素瘤B16-F0细胞增殖的影响及其分子机制。方法：采用RNA干扰在B16-F0细胞中基因沉默NCAM，通过MTT和软琼脂克隆形成实验考察细胞增殖能力的变化；通过小鼠皮下肿瘤移植实验考察体内黑色素瘤生长的变化；使用免疫印迹筛选出受NCAM影响的信号分子，在此基础上使用RNA干扰和高表达实验确定介导NCAM调控增殖的主要信号分子。结果：NCAM基因沉默后B16-F0细胞的增殖能力和克隆形成能力明显降低，细胞在小鼠皮下形成的黑色素瘤的生长也明显受到抑制。其中，β-catenin介导了NCAM对于B16-F0细胞增殖的调控，但NCAM对于β-catenin的调控不依赖于经典的Wnt通路。结论：NCAM通过Wnt非依赖性的β-catenin通路促进小鼠黑色素瘤细胞的增殖。

Neural cell adhesion molecule promotes proliferation of mouse melanoma B16-F0 cells via β-catenin independent of canonical Wnt pathway

AIM：To investigate the effects of neural cell adhesion molecule (NCAM) on the proliferation of mouse melanoma B16-F0 cells, and to further explore the involved signaling pathways. METHODS：RNA interference was used to silence the expression of NCAM in B16-F0 cells, followd by MTT and soft agar assays to evaluate the proliferation. Subcutaneous transplatation of NCAM-silencing B16-F0 cells into C57BL/6J mice was performed, and the tumor growth in vivo was observed. Western blotting was used to clarify the involved signaling pathways. RESULTS：The proliferation and colony formation of B16-F0 cells in vitro and the growth of transplanted melanoma in vivo were significantly inhibited by NCAM siRNA. Interestingly, the change of NCAM expression level markedly regulated the activity of β-catenin, and this signaling pathway was independent of canonical Wnt pathway. CONCLUSION：Our findings reveal a novel regulatory role of NCAM in the progression of melanoma, which might serve as a new therapeutic target for the treatment of melanoma.