Guo Li-Li, He Zhao-Cai, Yang Chang-Qing, Qiao Pei-Tang, Yin Guo-Ling
Department of Gastroenterology, Heping Hospital, Changzhi Medical College, Changzhi, Shanxi 046000, China.
Department of General Surgery, Heping Hospital, Changzhi Medical College, Changzhi, Shanxi 046000, China.
BMB Rep. 2015 Nov;48(11):630-5. doi: 10.5483/bmbrep.2015.48.11.130.
Downregulation of olfactomedin-4 (OLFM4) is associated with tumor progression, lymph node invasion and metastases. However, whether or not downregulation of OLFM4 is associated with epigenetic silencing remains unknown. In this study, we investigate the role of OLFM4 in gastric cancer cell invasion. We confirm the previous result that OLFM4 expression is increased in gastric cancer tissues and decreases with an increasing number of metastatic lymph nodes, which are associated with OLFM4 promoter hypermethylation. Overexpression of OLFM4 in gastric cancer cells had an inhibitory effect on cell invasion. Furthermore, we found that focal adhesion kinase (FAK) was negatively correlated with OLFM4 in regards to lymph node metastasis in gastric cancer tissues. Also, inhibition of FAK induced by OLFM4 knockdown resulted in a decrease in cell invasion. Thus, our study demonstrates that epigenetic silencing of OLFM4 enhances gastric cancer cell invasion via activation of FAK signaling.
嗅觉介质-4(OLFM4)的下调与肿瘤进展、淋巴结侵袭和转移相关。然而,OLFM4的下调是否与表观遗传沉默相关仍不清楚。在本研究中,我们调查了OLFM4在胃癌细胞侵袭中的作用。我们证实了先前的结果,即OLFM4在胃癌组织中的表达增加,并随着转移淋巴结数量的增加而降低,这与OLFM4启动子高甲基化有关。OLFM4在胃癌细胞中的过表达对细胞侵袭有抑制作用。此外,我们发现,在胃癌组织的淋巴结转移方面,粘着斑激酶(FAK)与OLFM4呈负相关。而且,OLFM4敲低诱导的FAK抑制导致细胞侵袭减少。因此,我们的研究表明,OLFM4的表观遗传沉默通过激活FAK信号增强胃癌细胞侵袭。