Liao Tian, Wen Duo, Ma Ben, Hu Jia-Qian, Qu Ning, Shi Rong-Liang, Liu Liang, Guan Qing, Li Duan-Shu, Ji Qing-Hai
Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Department of Breast Surgery, Breast Cancer Institute, Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Oncotarget. 2017 Feb 14;8(7):11719-11728. doi: 10.18632/oncotarget.14319.
Yes-associated protein 1 (YAP1) stimulates cell proliferation, epithelial-to-mesenchymal transition, invasion and metastasis in several cancers. Here, we investigated the involvement of YAP1 in papillary thyroid carcinoma (PTC) by assessing YAP1 mRNA and protein levels in PTC tissues and matched normal thyroid epithelial tissues from 50 patients. YAP1 mRNA and protein levels were higher in PTC tumor tissues than in control tissues, and correlated positively with the levels of proliferation-related genes (KI67 and c-MYC). We also used lentiviral vectors to overexpress or silence YAP1 expression in the K1 PTC cell line so that we could investigate the effects of YAP1 on cancer cell proliferation. YAP1 overexpression enhanced PTC cell proliferation by activating ERK1/2 and AKT, and these effects were impaired by treating the cells with the MEK inhibitor U0126 or the AKT inhibitor GSK690693. Finally, YAP1 overexpression dramatically induced growth of tumors from PTC cells in a xenograft mouse model. These results suggest that YAP1 enhances cell proliferation in PTC, and thus may be a promising target in the treatment of PTC.
Yes相关蛋白1（YAP1）在多种癌症中可刺激细胞增殖、上皮-间质转化、侵袭和转移。在此，我们通过评估50例患者的甲状腺乳头状癌（PTC）组织及配对的正常甲状腺上皮组织中YAP1的mRNA和蛋白水平，来研究YAP1在PTC中的作用。PTC肿瘤组织中YAP1的mRNA和蛋白水平高于对照组织，且与增殖相关基因（KI67和c-MYC）的水平呈正相关。我们还使用慢病毒载体在K1 PTC细胞系中过表达或沉默YAP1的表达，以便研究YAP1对癌细胞增殖的影响。YAP1的过表达通过激活ERK1/2和AKT增强了PTC细胞的增殖，而用MEK抑制剂U0126或AKT抑制剂GSK690693处理细胞会削弱这些作用。最后，YAP1的过表达在异种移植小鼠模型中显著诱导了PTC细胞肿瘤的生长。这些结果表明，YAP1增强了PTC中的细胞增殖，因此可能是PTC治疗中一个有前景的靶点。
