Liu Junguang, Yan Peiyun, Jing Niancai, Yang Jili
Department of General Surgery, Wendeng Central Hospital, Wendeng, Shandong Province, 264400, China.
Tumour Biol. 2014 Aug;35(8):8161-7. doi: 10.1007/s13277-014-2066-y. Epub 2014 May 21.
Colorectal cancer (CRC) is the third leading cause of cancer mortality in the world. We report that one oncogene amplified on chromosome 3q26, LMO1, a master transcriptional regulator of stemness, operates to drive strong growth phenotype in CRC. The gene expression changes of LMO1 in human CRC tissues compared with noncancerous tissues were detected using real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohistochemistry, which identified the gene overexpression of LMO1 in CRC. Moreover, we discovered that LMO1 promoted cancer cell proliferation in vitro/in vivo and LMO1 expression correlated with elevated AKT phosphorylation in CRC while the AKT phosphorylation was required for oncogenic effects of LMO1. Next, our data point to the usefulness of LMO1 overexpression, as a new predictive marker for responsiveness to cetuximab. All in all, LMO1 is a commonly activated tumor promoter that activates AKT signaling in CRC and a new predictive marker for targeted therapy.
结直肠癌(CRC)是全球癌症死亡的第三大主要原因。我们报告称,位于3q26染色体上的一个癌基因LMO1,作为干性的主要转录调节因子,在CRC中发挥作用以驱动强烈的生长表型。使用实时定量逆转录聚合酶链反应(QRT-PCR)分析和免疫组织化学检测了人CRC组织与非癌组织中LMO1的基因表达变化,结果确定了LMO1在CRC中的基因过表达。此外,我们发现LMO1在体外/体内促进癌细胞增殖,并且LMO1表达与CRC中AKT磷酸化升高相关,而AKT磷酸化是LMO1致癌作用所必需的。接下来,我们的数据表明LMO1过表达作为西妥昔单抗反应性的新预测标志物具有实用性。总而言之,LMO1是一种在CRC中激活AKT信号传导的常见激活型肿瘤促进因子,也是靶向治疗的新预测标志物。