MTA1 overexpression induces cisplatin resistance in nasopharyngeal carcinoma by promoting cancer stem cells properties.
MTA1 overexpression induces cisplatin resistance in nasopharyngeal carcinoma by promoting cancer stem cells properties.
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DOI：
10.14348/molcells.2014.0029
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发表时间：
2014-09
影响因子：
3.8
通讯作者：
Huang J
中科院分区：
文献类型：
--
作者：
Feng X;Zhang Q;Xia S;Xia B;Zhang Y;Deng X;Su W;Huang J
转移相关基因1(MTA1)癌基因被认为参与了肿瘤进展的调控。然而，仍然没有直接证据表明MTA1调节顺铂(CDDP)耐药性以及癌症干细胞特性。在本研究中，我们发现MTA1在CNE1/CDDP细胞中富含。敲除CNE1/CDDP细胞中MTA1基因可逆转CSCs的特性和对CDDP的耐药。然而，MTA1在CNE1细胞中的异位表达诱导了CSCs表型和CDDP不敏感。有趣的是，LY294002抑制PI3K/Akt后，CNE1细胞中MTA1诱导的CSCs特性和CDDP耐药的异位过表达被逆转。此外，CNE1/CDDP细胞的MTA1表达和Akt活性明显高于CNE1细胞。这些结果表明，MTA1可能通过PI3K/Akt信号通路调节肿瘤干细胞的特性，在促进鼻咽癌细胞对顺铂的耐药性中发挥关键作用。我们的研究结果表明，MTA1可能成为鼻咽癌治疗中克服顺铂耐药的潜在靶点。
Themetastasis-associated gene 1 (MTA1) oncogene hasbeen suggested to be involved in the regulation of cancer progression. However, there is still no direct evidence that MTA1 regulates cisplatin (CDDP) resistance, as well as cancer stem cell properties. In this study, we found that MTA1 was enriched in CNE1/CDDP cells. Knock down of MTA1 in CNE1/CDDP cells reversed CSCs properties and CDDP resistance. However, ectopic expression of MTA1 in CNE1 cells induced CSCs phenotypes and CDDP insensitivity. Interestingly, ectopic overexpression of MTA1-induced CSCs properties and CDDP resistance were reversed in CNE1 cells after inhibition of PI3K/Akt by LY294002. In addition, MTA1 expression and Akt activity in CNE1/CDDP cells was much higher than that in CNE1 cells. These results suggested that MTA1 may play a critical role in promoting CDDP resistance in NPC cells by regulatingcancer stem cell properties via thePI3K/Akt signaling pathway. Our findings suggested that MTA1 may be a potential target for overcoming CDDP resistance in NPC therapy.