Proteomic identification of keratin alterations with enhanced proliferation of oral carcinoma cells by loss of mucosa-associated lymphoid tissue 1 expression.
Proteomic identification of keratin alterations with enhanced proliferation of oral carcinoma cells by loss of mucosa-associated lymphoid tissue 1 expression.
复制标题
DOI：
10.3892/ijo.2013.1990
复制
发表时间：
2013-09
影响因子：
5.2
通讯作者：
Y. Kawamoto;Y. Ohyama;T. Chiba;H. Yagishita;H. Sakashita;K. Imai
中科院分区：
文献类型：
--
作者：
Y. Kawamoto;Y. Ohyama;T. Chiba;H. Yagishita;H. Sakashita;K. Imai
口腔癌的进展与在已建立或未知途径中起作用的分子的异常激活和失活相关。尽管在正常口腔上皮中表达的粘膜相关淋巴组织1（MALT 1）在预后较差的侵袭性癌亚组中失活，但表达缺失后癌细胞的表型变化尚不清楚。我们进行了蛋白质组学分析，以确定口腔癌细胞中MALT 1调节的蛋白质。四种不同的角蛋白包括在十个最丰富的变化蛋白质。K8/18在MALT 1稳定表达的癌细胞中上调，K5/14在MALT 1边缘对照细胞中上调。K8/18上调和K5/14下调具有MALT 1剂量依赖性，并在一系列口腔癌细胞中观察到。MALT 1抑制细胞增殖（0.52倍，P<0.01），其显性阴性形式促进细胞增殖（1.33倍，P<0.01）。细胞增殖的降低与细胞周期蛋白D1的减少有关，而细胞周期蛋白D1的减少可通过针对MALT 1的短干扰RNA恢复。两者合计，MALT 1表达的损失改变角蛋白的表达和增强癌细胞的增殖，并可能进展到先进的口腔癌状态。
Progression of oral carcinomas associates with aberrant activation and inactivation of molecules that work in established or unknown pathways. Although mucosa‑associated lymphoid tissue 1 (MALT1) expressed in normal oral epithelium is inactivated in the aggressive subset of carcinomas with worse prognosis, phenotypic changes of carcinoma cells upon the loss of expression is unknown. We performed a proteomic analysis to identify MALT1‑regulated proteins in oral carcinoma cells. Four different keratins were included in the ten most abundantly changed proteins. K8/18 were upregulated in MALT1 stably‑expressing carcinoma cells and K5/14 in MALT1‑marginal control cells. K8/18 upregulation and K5/14 downregulation were MALT1 dose‑dependent and observed in a series of oral carcinoma cells. MALT1 suppressed cell proliferation (0.52-fold, P<0.01) and its dominant-negative form stimulated it (1.33-fold, P<0.01). The decreased proliferation associated with reduction of cyclin D1, which was recovered by the short interfering RNA against MALT1. Taken together, loss of MALT1 expression alters keratin expression and enhances proliferation of carcinoma cells, and may progress oral carcinomas into the advanced state.