Effects of downregulated HDAC6 expression on the proliferation of lung cancer cells
Effects of downregulated HDAC6 expression on the proliferation of lung cancer cells
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DOI：
10.1016/j.bbrc.2008.06.092
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发表时间：
2008-09-12
影响因子：
3.1
通讯作者：
Yoshida, Minoru
中科院分区：
文献类型：
--
作者：
Kamemura, Kazuo;Ito, Akihiro;Yoshida, Minoru
组蛋白脱乙酰基酶6（HDAC6）是一种多功能的细胞溶质蛋白脱乙酰基酶，其主要作用于微管蛋白。在这里，我们报告了HDAC6表达的稳定敲低导致A549肺癌细胞中受体酪氨酸激酶（如表皮生长因子受体（EGFR）和血小板衍生生长因子受体α）的稳态水平降低。HDAC6敲减细胞中EGFR水平的降低与微管乙酰化的增加相关，这是由于EGFR蛋白的周转增加。尽管EGFR水平降低，但缺乏功能性HDAC6的A549细胞似乎正常生长，这可能是由于细胞外信号调节激酶1和2的表达增加。事实上，HDAC6敲低细胞比对照细胞对MEK抑制剂U0126更敏感。这些结果表明，HDAC6抑制剂与生长因子信号传导抑制剂组合可用作癌症治疗。(C)2008年爱思唯尔公司All rights reserved.
Histone deacetylase 6 (HDAC6) is a Multifunctional, cytosolic protein deacetylase that primarily acts on 0(tubulin. Here we report that stable knockdown of HDAC6 expression causes a decrease in the steady-state level of receptor tyrosine kinases, Such as epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor alpha, in A549 lung cancer cells. The decreased levels of in EGFR in HDAC6-knockdown cells, which correlated with increased acetylation of microtubules, were due to increased turnover of EGFR protein. Despite the decrease in EGFR levels, A549 cells lacking functional HDAC6 appeared to grow normally, probably due to increased expression of extracellular signal-regulated kinases 1 and 2. Indeed, HDAC6-knockdown cells were more sensitive than control cells to the MEK inhibitor U0126. These results suggest that HDAC6 inhibitors combined with inhibitors of growth factor signaling may be useful as cancer therapy. (C) 2008 Elsevier Inc. All rights reserved.