Identification of Sox6 as a regulator of pancreatic cancer development.
Identification of Sox6 as a regulator of pancreatic cancer development.
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鉴定 Sox6 作为胰腺癌发展的调节因子
DOI：
10.1111/jcmm.13470
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发表时间：
2018-03
影响因子：
5.3
通讯作者：
Yang L
中科院分区：
文献类型：
--
作者：
Jiang W;Yuan Q;Jiang Y;Huang L;Chen C;Hu G;Wan R;Wang X;Yang L
胰腺癌（PC）是一种侵袭性恶性肿瘤，预后差，对化疗和放疗的反应性低。大多数PC患者在诊断时有转移性疾病，这部分解释了这种疾病的高死亡率。在这里，我们探讨了转录因子性别决定区Y盒（Sox）6在PC细胞侵袭性中的作用。我们发现Sox 6在PC患者中下调与转移性疾病相关。Sox 6过表达抑制PC细胞增殖和迁移在体外和肿瘤生长和肝转移在体内。Sox 6抑制上皮间质转化（EMT）和Akt信号传导。Sox 6被证明与Twist 1的启动子相互作用，Twist 1是一种参与诱导EMT的螺旋-环-螺旋转录因子，并通过将组蛋白去乙酰化酶1募集到Twist 1基因的启动子来调节Twist 1的表达。Twist 1过表达逆转了Sox 6抑制EMT的作用，证实了Sox 6抑制肿瘤侵袭的作用是通过Twist 1表达的调节介导的。这些结果表明，PC细胞的侵略性行为的一种新的机制，并确定潜在的治疗PC的治疗靶点。
Pancreatic cancer (PC) is an aggressive malignancy associated with a poor prognosis and low responsiveness to chemotherapy and radiotherapy. Most patients with PC have metastatic disease at diagnosis, which partly accounts for the high mortality from this disease. Here, we explored the role of the transcription factor sex‐determining region Y‐box (Sox) 6 in the invasiveness of PC cells. We showed that Sox6 is down‐regulated in patients with PC in association with metastatic disease. Sox6 overexpression suppressed PC cell proliferation and migration in vitro and tumour growth and liver metastasis in vivo. Sox6 inhibited epithelial‐mesenchymal transition (EMT), and Akt signalling. Sox6 was shown to interact with the promoter of Twist1, a helix–loop–helix transcription factor involved in the induction of EMT, and to modulate the expression of Twist1 by recruiting histone deacetylase 1 to the promoter of the Twist1 gene. Twist1 overexpression reversed the effect of Sox6 on inhibiting EMT, confirming that the effect of Sox6 on suppressing tumour invasiveness is mediated by the modulation of Twist1 expression. These results suggest a novel mechanism underlying the aggressive behaviour of PC cells and identify potential therapeutic targets for the treatment of PC.
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影响因子：
2.5
作者：
Hagiwara, Nobuko
通讯作者：
Hagiwara, Nobuko
影响因子：
254.7
作者：
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影响因子：
64.5
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作者：
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影响因子：
3.4
作者：
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通讯作者：
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