Liu Jia Yun, Wu Xiao Yu, Wu Guan Nan, Liu Fu-Kun, Yao Xue-Quan
Department of Surgical Oncology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine155 Hanzhong Road, Gulou District, Nanjing, China.
Am J Transl Res. 2017 May 15;9(5):2207-2218. eCollection 2017.
Colorectal cancer is one of the major health problems, with invade surrounding tissues, and migrate to distant organs being the most critical concern, thus identified metastasis associated hallmarks and more efficacious treatment are urgently needed. It found that forkhead box q1 (FOXQ1) is aberrant expression in variety of human cancers and FOXQ1 is involved in oncogenic pathways. However, the role of FOXQ1 has been unexplored in colorectal cancer metastasis to date. Here, expression of FOXQ1 was higher in colorectal cancer tissue samples and cancer cell lines than in normal colorectal tissue and cell lines. Further research suggested that FOXQ1 positively regulated cell proliferation in colorectal cancer and down-regulation of CDK6, extracellular regulated protein kinases 1/2 (ERK1/2) and mammalian target of rapamycin (mTOR). In corresponding to this result, over-expression of FOXQ1 significantly promoted colorectal cancer growth in vivo. Moreover, down regulation of FOXQ1 expression in colorectal carcinoma cell HCT116 and LOVO strikingly inhibits tumor growth in vivo. Finally, FOXQ1-dependent inhibition of colorectal cancer cell migration and invasion and down-regulation of focal adhesion kinase (FAK), phosphatidyl inositol 3-kinase (PI3K) phosphorylation, AKT (v-akt murine thymoma viral oncogene) phosphorylation and matrix metalloproteinase-2/9 (MMP-2/9) expression. These integrated efforts have identified FOXQ1 as a tumor promoter and might provide promising approaches for colorectal cancer metastasis treatment.
结直肠癌是主要的健康问题之一，其侵袭周围组织并转移至远处器官是最为关键的问题，因此迫切需要确定与转移相关的特征并找到更有效的治疗方法。研究发现，叉头框Q1（FOXQ1）在多种人类癌症中表达异常，且参与致癌途径。然而，迄今为止，FOXQ1在结直肠癌转移中的作用尚未得到探索。在此，结直肠癌组织样本和癌细胞系中FOXQ1的表达高于正常结直肠组织和细胞系。进一步研究表明，FOXQ1在结直肠癌中正向调节细胞增殖，并下调细胞周期蛋白依赖性激酶6（CDK6）、细胞外调节蛋白激酶1/2（ERK1/2）和雷帕霉素靶蛋白（mTOR）。与此结果相应，FOXQ1的过表达在体内显著促进结直肠癌生长。此外，在结直肠癌细胞HCT116和LOVO中下调FOXQ1表达可显著抑制体内肿瘤生长。最后，FOXQ1依赖性抑制结直肠癌细胞迁移和侵袭，并下调粘着斑激酶（FAK）、磷脂酰肌醇3激酶（PI3K）磷酸化、AKT（v-akt小鼠胸腺瘤病毒癌基因）磷酸化和基质金属蛋白酶-2/9（MMP-2/9）表达。这些综合研究确定FOXQ1为肿瘤促进因子，并可能为结直肠癌转移治疗提供有前景的方法。
