Department of General Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.
Oncol Rep. 2013 Sep;30(3):1355-61. doi: 10.3892/or.2013.2544. Epub 2013 Jun 19.
Liver metastasis is a major cause of mortality for colorectal cancer (CRC). However, the underlying mechanisms remain largely unknown. GATA binding protein 6 (GATA6), a zinc-finger transcription factor, is expressed in the colorectal epithelium. We investigated the clinical significance of GATA6 and its role in invasion and metastasis in CRC. Expression of GATA6 in 89 cancerous, 35 adjacent normal and 39 liver metastatic samples from 89 CRC patients undergoing surgical resection was detected by immunohistochemical (IHC) methods. The effect of GATA6 on invasion and metastasis was assessed in CRC cells by shRNA lentivirus or expressed-plasmid transfection. We found that GATA6 expression was significantly higher in liver metastatic tissues compared with adjacent normal tissues. Aberrant GATA6 expression in CRC was associated with liver metastasis. Kaplan-Meier analysis showed GATA6 expression correlated with poor overall survival (OS) in CRC. The cell invasion and migration of established CRC cell lines were decreased by GATA6 knockdown and enhanced by GATA6 overexpression in vitro. Thus, aberrant expression of GATA6 correlates with poor prognosis and liver metastasis in CRC.
肝转移是结直肠癌（CRC）患者死亡的主要原因。然而，其潜在机制在很大程度上尚不清楚。GATA 结合蛋白 6（GATA6）是一种锌指转录因子，在结直肠上皮中表达。我们研究了 GATA6 的临床意义及其在 CRC 侵袭和转移中的作用。通过免疫组织化学（IHC）方法检测了 89 例 CRC 患者手术切除的 89 例癌组织、35 例癌旁正常组织和 39 例肝转移组织中 GATA6 的表达。通过 shRNA 慢病毒或表达质粒转染评估 GATA6 对 CRC 细胞侵袭和转移的影响。我们发现 GATA6 在肝转移组织中的表达明显高于癌旁正常组织。CRC 中异常的 GATA6 表达与肝转移有关。Kaplan-Meier 分析显示，GATA6 表达与 CRC 的总生存期（OS）不良相关。在体外，GATA6 的敲低降低了已建立的 CRC 细胞系的细胞侵袭和迁移，而过表达 GATA6 则增强了其侵袭和迁移。因此，GATA6 的异常表达与 CRC 的不良预后和肝转移相关。
