MTA3 Represses Cancer Stemness by Targeting the SOX2OT/SOX2 Axis
MTA3 Represses Cancer Stemness by Targeting the SOX2OT/SOX2 Axis
复制标题
MTA3 通过靶向 SOX2OT/SOX2 轴抑制癌症干性
DOI：
10.1016/j.isci.2019.11.009
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发表时间：
2019-12-20
期刊：
影响因子：
5.8
通讯作者：
Zhang, Hao
中科院分区：
文献类型：
--
作者：
Du, Liang;Wang, Lu;Zhang, Hao
癌细胞干细胞性（CCS）在恶性肿瘤的维持和转移中起着关键作用，但其分子机制还远未完全阐明。尽管SOX 2在癌症发展和CCS中的重要性已得到公认，但MTA 3在这些过程中的作用尚不清楚。在这项研究中，我们使用食管鳞状细胞癌（ESCC）作为模型系统，以证明MTA 3可以抑制CCS和转移在体外和体内。从机制上讲，通过与GATA 3形成抑制性复合物，MTA 3下调SOX 2 OT，随后抑制SOX 2 OT/SOX 2轴，并最终抑制CCS和转移。更重要的是，MTA 3（低）/SOX 2（高）与预后不良相关，可作为独立的预后因素。这些结果表明，MTA 3/SOX 2 OT/SOX 2轴在CCS中起着不可或缺的作用。因此，该轴可以潜在地用于癌症分层并用作治疗靶点。
Cancer cell stemness (CCS) plays critical roles in bothmalignancy maintenance andmetastasis, yet the underlying molecular mechanisms are far from complete. Although the importance of SOX2 in cancer development and CCS are well recognized, the role of MTA3 in these processes is unknown. In this study, we used esophageal squamous cell carcinoma (ESCC) as a model system to demonstrate that MTA3 can repress both CCS and metastasis in vitro and in vivo. Mechanistically, by forming a repressive complex with GATA3, MTA3 downregulates SOX2OT, subsequently suppresses the SOX2OT/SOX2 axis, and ultimately represses CCS and metastasis. More importantly, MTA3(low)/SOX2(high) is associated with poor prognosis and could serve as an independent prognostic factor. These findings altogether indicate that MTA3/SOX2OT/SOX2 axis plays an indispensable role in CCS. Therefore, this axis could be potentially used in cancer stratification and serves as a therapeutic target.