FERMT1 敲低通过使 PI3K/AKT 信号通路失活来抑制口腔鳞状细胞癌细胞上皮-间充质转化。
FERMT1 knockdown inhibits oral squamous cell carcinoma cell epithelial-mesenchymal transition by inactivating the PI3K/AKT signaling pathway.
机构信息
Department of Stomatology, The First Affiliated Hospital, Guangxi University of Science and Technology, Liuzhou, 545006, China.
Medical College, Medical Experimental Center, Guangxi University of Science and Technology, Building D, 257 Liushi Road, Yufeng District, Liuzhou, 545006, China.
出版信息
BMC Oral Health. 2021 Nov 23;21(1):598. doi: 10.1186/s12903-021-01955-9.
BACKGROUND
The metastasis of oral cancer is one of the main causes of death. However, the mechanisms underlying oral cancer metastasis have not been completely elucidated. Fermitin family member 1 (FERMT1) plays an -oncogene role in many cancers; however, the role of FERMT1 in oral squamous cell cancer (OSCC) remains unclear.
METHODS
In this study, OSCC cells were treated with 5 ng/ml recombinant human Transforming growth factor-β1 (TGF-β1) protein. FERMT1 expression was measured in OSCC cell lines by RT-qPCR and western blotting. The effect of FERMT1 knockdown on the migration and invasion of OSCC cells was evaluated by Transwell assay. The epithelial-mesenchymal transition (EMT) and PI3K/AKT signaling pathway-related mRNA expression and protein levels were assessed by RT-qPCR and western blotting.
RESULTS
We found that FERMT1 expression was elevated in TGF-β1-induced OSCC cell lines, and knockdown of FERMT1 inhibited the migration and invasion in TGF-β1-induced OSCC cells. FERMT1 silencing inhibited vimentin, N-cadherin, matrix metalloproteinase 9 (MMP-9) expression and promoted E-cadherin expression, suggesting that FERMT1 silencing inhibited EMT in TGF-β1-induced OSCC cells. Furthermore, FERMT1 silencing inactivated the PI3K/AKT signaling pathway in TGF-β1-induced OSCC cells. Activation of the PI3K/AKT signaling pathway reversed the effect of FERMT1 silencing on OSCC cell migration, invasion, and EMT.
CONCLUSIONS
FERMT1 silencing inhibits the migration, invasion, and EMT of OSCC cells via inactivation of the PI3K/AKT signaling pathway, suggesting that FERMT1 is a novel and potential therapeutic target for anti-metastatic strategies for OSCC.
背景
口腔癌的转移是导致死亡的主要原因之一。然而，口腔癌转移的机制尚未完全阐明。FERM 结构域包含 1 型（FERM）家族成员 1（FERMT1）在许多癌症中发挥癌基因作用；然而，FERMT1 在口腔鳞状细胞癌（OSCC）中的作用尚不清楚。
方法
在这项研究中，用 5ng/ml 重组人转化生长因子-β1（TGF-β1）蛋白处理 OSCC 细胞。通过 RT-qPCR 和 Western blot 检测 OSCC 细胞系中 FERMT1 的表达。通过 Transwell 测定评估 FERMT1 敲低对 OSCC 细胞迁移和侵袭的影响。通过 RT-qPCR 和 Western blot 评估上皮-间充质转化（EMT）和 PI3K/AKT 信号通路相关 mRNA 表达和蛋白水平。
结果
我们发现 FERMT1 在 TGF-β1 诱导的 OSCC 细胞系中表达上调，FERMT1 敲低抑制 TGF-β1 诱导的 OSCC 细胞的迁移和侵袭。FERMT1 沉默抑制波形蛋白、N-钙黏蛋白、基质金属蛋白酶 9（MMP-9）的表达，促进 E-钙黏蛋白的表达，表明 FERMT1 沉默抑制 TGF-β1 诱导的 OSCC 细胞 EMT。此外，FERMT1 沉默使 TGF-β1 诱导的 OSCC 细胞中的 PI3K/AKT 信号通路失活。激活 PI3K/AKT 信号通路逆转了 FERMT1 沉默对 OSCC 细胞迁移、侵袭和 EMT 的影响。
结论
FERMT1 沉默通过抑制 PI3K/AKT 信号通路抑制 OSCC 细胞的迁移、侵袭和 EMT，表明 FERMT1 是 OSCC 抗转移策略的一个新的潜在治疗靶点。
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