Department of Colorectal Surgery, Affiliated Union Hospital of Fujian Medical University, Fuzhou, Fujian, PR China.
Oncol Rep. 2012 Jul;28(1):179-85. doi: 10.3892/or.2012.1751. Epub 2012 Apr 2.
WW domain-containing transcription regulator 1 (WWTR1) was initially identified as a transcriptional coactivator involved in the differentiation of stem cells as well as the development of multiple organs. Recently, WWTR1 has also been identified as a major component of the novel Hippo signalling pathway important for the development of breast and lung cancer. Here, we show for the first time that WWTR1 has an oncogenic function in colorectal cancer cell lines. Knockdown of WWTR1 by lentivirus-mediated RNA interference in human colorectal cancer cells significantly decreased cell proliferation and the colony formation of RKO cells in vitro and tumor growth in vivo. Furthermore, we found that the decreased proliferation was due to cell cycle arrest and increased apoptosis. In addition, efficient knockdown of WWTR1, demonstrated by quantitative real-time PCR, led to upregulation of ASNS and downregulation of SMAD3, LTBR, BAX and BAK1 in WWTR1 knockdown cells, suggesting that these genes may be involved in the repression of cell proliferation. Our findings indicate that WWTR1 is an oncogene and has an important role in the proliferation of colorectal cancer cells and in tumor growth in vivo.
WW 结构域包含转录调节因子 1（WWTR1）最初被鉴定为一种转录共激活因子，参与干细胞的分化以及多个器官的发育。最近，WWTR1 也被确定为新的 Hippo 信号通路的主要组成部分，该通路对乳腺癌和肺癌的发生发展很重要。在这里，我们首次表明 WWTR1 在结直肠癌细胞系中具有致癌功能。通过慢病毒介导的 RNA 干扰敲低人结直肠癌细胞中的 WWTR1，显著降低了 RKO 细胞的体外增殖和集落形成以及体内肿瘤生长。此外，我们发现增殖减少是由于细胞周期停滞和凋亡增加所致。此外，通过实时定量 PCR 证实的 WWTR1 的有效敲低导致 WWTR1 敲低细胞中 ASNS 的上调和 SMAD3、LTBR、BAX 和 BAK1 的下调，表明这些基因可能参与抑制细胞增殖。我们的研究结果表明，WWTR1 是一种致癌基因，在结直肠癌细胞的增殖和体内肿瘤生长中起重要作用。
