Neoplasma. 2014;61(2):128-35. doi: 10.4149/neo_2014_018.
Though the overall incidence of gastric cancer was decreasing in the developed countries in the past decades, it is still a serious threat to human health throughout the world. The molecular mechanisms underlying development of gastric cancer remains unclear. Though accumulating evidences shed a light on the implications of mitochondrial tumor suppressor (MTUS1) in carcinogenesis, the functional role of MTUS1 in regulation of proliferation and metastasis of gastric cancer cell is still poorly understood. In this study, we showed that the level of MTUS1 expression is relatively low in gastric cancer cell lines compared to normal gastric epithelial cells. By using clinical samples, we found that MTUS1 expression is downregulated in tumor tissues compared to non-cancerous counterpart, and loss of MTUS1 was associated with high incidence of lymph node metastasis and poor patient outcome. Moreover, we demonstrate that MTUS1 has a significant impact on both the proliferative and metastatic potential of gastric cancer cell line, which were further supported by using mice tumor xenograft models. The present data suggested MTUS1 as a potential tumor suppressor in gastric cancer and might lead to a better understanding of gastric carcinogenesis.
尽管在过去几十年中,发达国家的胃癌总体发病率呈下降趋势,但胃癌仍是全世界人类健康的严重威胁。胃癌发生的分子机制仍不清楚。尽管越来越多的证据表明线粒体肿瘤抑制因子(MTUS1)在肿瘤发生中的意义,但 MTUS1 在调节胃癌细胞增殖和转移中的功能作用仍知之甚少。在这项研究中,我们发现与正常胃上皮细胞相比,胃癌细胞系中 MTUS1 的表达水平相对较低。通过使用临床样本,我们发现与非癌组织相比,肿瘤组织中 MTUS1 的表达下调,并且 MTUS1 的缺失与淋巴结转移发生率高和患者预后不良相关。此外,我们还证明 MTUS1 对胃癌细胞系的增殖和转移潜能有显著影响,这一结果进一步通过小鼠肿瘤异种移植模型得到支持。这些数据表明 MTUS1 是胃癌的潜在肿瘤抑制因子,并可能有助于更好地理解胃癌的发生机制。