Expression of TMEM207 in Colorectal Cancer: Relation between TMEM207 and Intelectin-1.
Expression of TMEM207 in Colorectal Cancer: Relation between TMEM207 and Intelectin-1.
复制标题
DOI：
10.7150/jca.13732
复制
发表时间：
2016
影响因子：
3.9
通讯作者：
Takeuchi T
中科院分区：
文献类型：
--
作者：
Maeda K;Saigo C;Kito Y;Sakuratani T;Yoshida K;Takeuchi T
最近的研究进展强调了肠杯状细胞产生的凝集素，intelectin-1（也称为omentin-1），作为肿瘤抑制剂。一项研究表明，intelectin-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为止尚未表征的跨膜蛋白TMEM 207在结直肠癌中的表达，我们发现TMEM 207的功能与intelectin-1的加工有关。用特异性抗体，在216例结直肠癌组织中检测到38例TMEM 207免疫反应性。TMEM 207免疫反应性与淋巴结转移状态呈负相关（p < 0.01）。TMEM 207的表达与大肠癌的粘液表型显著相关。免疫共沉淀试验揭示了结直肠癌细胞中intelectin-1和TMEM 207之间的相互作用。近端连接测定表明，intelectin-1和TMEM 207共定位于结肠直肠癌细胞的细胞质。小干扰RNA介导的TMEM 207敲低增加了培养的结直肠癌细胞中intelectin-1的多聚泛素化和蛋白酶体降解，并降低了intelectin-1的分泌。这些发现表明TMEM 207表达的缺失导致intelectin-1产生不足，从而促进结直肠癌发生。
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.