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MTA1 通过 Hedgehog 信号通路诱导上皮-间充质转化促进口腔鳞状细胞癌的侵袭和迁移。

MTA1 promotes the invasion and migration of oral squamous carcinoma by inducing epithelial-mesenchymal transition via the hedgehog signaling pathway.

机构信息

Department of Oncology, Liaocheng People's Hospital, Affiliated to Shandong University and Clinical School of Shandong First Medical University, Liaocheng, 252000, PR China.

Department of Mammary and Thyroidology, Liaocheng People's Hospital, Affiliated to Shandong University and Clinical School of Shandong First Medical University, Liaocheng, 252000, PR China.

出版信息

Exp Cell Res. 2019 Sep 1;382(1):111450. doi: 10.1016/j.yexcr.2019.05.031. Epub 2019 May 29.

Abstract

The metastasis-associated gene 1 (MTA1) has previously been recognized as an oncogene in many tumors, and aberrant MTA1 expression has been related to invasion and migration; however, its role and underlying molecular mechanism in oral squamous carcinoma (OSCC) remain largely unexplored. In this work, we determined the expression of MTA1 in OSCC tissues and cell lines. The effect of MTA1 on metastasis and the role of MTA1 in the epithelial-to-mesenchymal transition (EMT) of OSCC cells were evaluated by assays both in vitro and in vivo. We also identified the key Hedgehog signaling pathway-related protein involved in the MTA1-induced EMT. We found that MTA1 expression was upregulated and positively related to the metastasis in OSCC tissues and cell lines. MTA1 overexpression promoted OSCC invasion, migration, and induced EMT, while its silencing had the opposite effect both in vitro and in vivo. Additionally, our data further revealed the relevant molecular mechanism, Hedgehog(Hh) signaling pathway contributed to the effect of MTA1 on the aggressive phenotypes of OSCC cells.These findings indicate that MTA1 enhances OSCC cells invasion and migration by inducing EMT via the Hedgehog signaling pathway, which suggests MTA1 may be an effective anti-OSCC therapeutic target.

摘要

转移相关基因 1(MTA1)先前已被认为是许多肿瘤中的癌基因,异常的 MTA1 表达与侵袭和迁移有关;然而,其在口腔鳞状细胞癌(OSCC)中的作用和潜在分子机制在很大程度上仍未得到探索。在这项工作中,我们确定了 MTA1 在 OSCC 组织和细胞系中的表达。通过体外和体内实验评估了 MTA1 对转移的影响以及 MTA1 在 OSCC 细胞上皮间质转化(EMT)中的作用。我们还确定了参与 MTA1 诱导的 EMT 的关键 Hedgehog 信号通路相关蛋白。我们发现 MTA1 的表达上调,与 OSCC 组织和细胞系中的转移呈正相关。MTA1 过表达促进 OSCC 侵袭、迁移,并诱导 EMT,而其沉默在体外和体内均具有相反的效果。此外,我们的数据进一步揭示了相关的分子机制,Hedgehog(Hh)信号通路有助于 MTA1 对 OSCC 细胞侵袭表型的影响。这些发现表明,MTA1 通过 Hedgehog 信号通路诱导 EMT 增强了 OSCC 细胞的侵袭和迁移,这表明 MTA1 可能是一种有效的抗 OSCC 治疗靶点。

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