Department of Geratic Surgery, Central South University, Xiangya Road 87, Changsha, Hunan, 410008, People's Republic of China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, Hunan, 410008, People's Republic of China.
BMC Cancer. 2018 Oct 22;18(1):1020. doi: 10.1186/s12885-018-4931-3.
Metastasis is the main cause of death in patients with advanced stage colon cancer. Epithelial mesenchymal transition (EMT) plays an important role in invasion and metastasis. Actin-like 6A (ACTL6A) is vital for embryogenesis and differentiation and is also critical for metastasis and EMT in hepatocellular carcinoma, as observed in our previous study. In the present study, we further explored the role of ACTL6A in colon cancer metastasis.
ACTL6A expression levels were analyzed in normal colon, colon adenoma and colon cancer specimens using public databases and tissue samples. ACTL6A expression and its association with clinicopathologic features of colon cancer patients were also analyzed. ACTL6A-overexpression and ACTL6A-knockdown colon cancer cells were used to perform cytological experiments to explore the potential biological function of ACTL6A in metastasis and EMT in colon cancer.
The data from both the Gene Expression Omnibus (GEO) and Oncomine databases showed that ACTL6A expression levels in colon adenoma and cancer were higher than those in normal colon samples. The ACTL6A expression level in fresh colon cancer specimens was also higher than that in the corresponding adjacent normal colon specimens. Patients with high ACTL6A expression directly correlated with advanced pT status, distant metastasis, poor differentiation and microvascular/perineural invasion. ACTL6A overexpression promoted migration and invasion of colon cancer cells, whereas ACTL6A knockdown exhibited the opposite effect in vitro. Moreover, we demonstrated that ACTL6A promoted EMT in colon cancer cells in vitro.
Our findings indicate that ACTL6A exhibits pro-tumor function and acts as an EMT activator in colon cancer. ACTL6A may serve as a potential therapeutic target for colon cancer.
转移是晚期结肠癌患者死亡的主要原因。上皮-间质转化（EMT）在侵袭和转移中起重要作用。肌动蛋白样 6A（ACTL6A）对胚胎发生和分化至关重要，并且在我们之前的研究中观察到，它在肝癌的转移和 EMT 中也很关键。在本研究中，我们进一步探讨了 ACTL6A 在结肠癌转移中的作用。
使用公共数据库和组织样本分析正常结肠、结肠腺瘤和结肠癌标本中 ACTL6A 的表达水平。还分析了 ACTL6A 的表达及其与结肠癌患者临床病理特征的关系。使用 ACTL6A 过表达和 ACTL6A 敲低结肠癌细胞进行细胞学实验，以探索 ACTL6A 在结肠癌转移和 EMT 中的潜在生物学功能。
来自基因表达综合数据库（GEO）和 Oncomine 数据库的数据显示，结肠癌腺瘤和癌症中 ACTL6A 的表达水平高于正常结肠样本。新鲜结肠癌标本中的 ACTL6A 表达水平也高于相应的相邻正常结肠标本。高 ACTL6A 表达的患者与晚期 pT 状态、远处转移、分化不良和微血管/神经周围浸润直接相关。ACTL6A 过表达促进了结肠癌细胞的迁移和侵袭，而 ACTL6A 敲低则在体外表现出相反的效果。此外，我们证明了 ACTL6A 在体外促进了结肠癌细胞的 EMT。
我们的研究结果表明，ACTL6A 在结肠癌中表现出促肿瘤功能，并作为 EMT 激活剂发挥作用。ACTL6A 可能成为结肠癌的潜在治疗靶点。
