Maeda Kenichi, Saigo Chiemi, Kito Yusuke, Sakuratani Takuji, Yoshida Kazuhiro, Takeuchi Tamotsu
1. Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan.
2. Department of Pathology and Translational Research, Gifu University Graduate School of Medicine, Gifu, Japan.
J Cancer. 2016 Jan 1;7(2):207-13. doi: 10.7150/jca.13732. eCollection 2016.
Recent research advances highlighted an intestinal goblet cell-produced lectin, intelectin-1 (also known as omentin-1), as a tumor suppressor. One study indicated that downregulation of intelectin-1 may be related to the unfavorable prognosis among patients with colorectal carcinoma at an advanced stage. The present study was aimed at analyzing the expression of a hitherto uncharacterized transmembrane protein TMEM207 in colorectal carcinoma, and we found that the TMEM207 function is linked to intelectin-1 processing. With specific antibodies, TMEM207 immunoreactivity was detected in 38 of 216 colorectal cancer tissue samples. TMEM207 immunoreactivity correlated inversely with lymph node metastatic status (p < 0.01). TMEM207 expression significantly correlated with the mucinous phenotype of colorectal carcinoma. A coimmunoprecipitation assay revealed an interaction between intelectin-1 and TMEM207 in colorectal cancer cells. A proximal ligation assay indicated that intelectin-1 and TMEM207 were colocalized to the cytoplasm of the colorectal cancer cells. A small-interfering-RNA-mediated knockdown of TMEM207 increased polyubiquitination and proteasome degradation of intelectin-1 in cultured colorectal cancer cells and decreased intelectin-1 secretion. These findings indicate that a loss of TMEM207 expression leads to insufficient intelectin-1 production thus promoting colorectal carcinogenesis.
最近的研究进展突显了一种肠道杯状细胞产生的凝集素,即肝表达凝集素-1(也称为网膜素-1),它是一种肿瘤抑制因子。一项研究表明,肝表达凝集素-1的下调可能与晚期结直肠癌患者的不良预后有关。本研究旨在分析一种迄今未被描述的跨膜蛋白TMEM207在结直肠癌中的表达,我们发现TMEM207的功能与肝表达凝集素-1的加工有关。使用特异性抗体,在216例结直肠癌组织样本中的38例中检测到TMEM207免疫反应性。TMEM207免疫反应性与淋巴结转移状态呈负相关(p<0.01)。TMEM207表达与结直肠癌的黏液表型显著相关。免疫共沉淀分析显示在结直肠癌细胞中肝表达凝集素-1与TMEM207之间存在相互作用。邻近连接分析表明肝表达凝集素-1和TMEM207共定位于结直肠癌细胞的细胞质中。小干扰RNA介导的TMEM207敲低增加了培养的结直肠癌细胞中肝表达凝集素-1的多聚泛素化和蛋白酶体降解,并减少了肝表达凝集素-1的分泌。这些发现表明TMEM207表达缺失导致肝表达凝集素-1产生不足,从而促进结直肠癌的发生。