Cellular stress induces cancer stem-like cells through expression of DNAJB8 by activation of heat shock factor 1.
Cellular stress induces cancer stem-like cells through expression of DNAJB8 by activation of heat shock factor 1.
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DOI：
10.1111/cas.13501
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发表时间：
2018-03
期刊：
影响因子：
5.7
通讯作者：
Torigoe T
中科院分区：
文献类型：
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作者：
Kusumoto H;Hirohashi Y;Nishizawa S;Yamashita M;Yasuda K;Murai A;Takaya A;Mori T;Kubo T;Nakatsugawa M;Kanaseki T;Tsukahara T;Kondo T;Sato N;Hara I;Torigoe T
在先前的研究中，我们发现热休克蛋白（HSP）40家族成员DNAJB 8在肾癌干细胞（CSC）/癌症起始细胞（CIC）中表达，并且它在维持肾脏CSC/CIC中发挥作用。热休克因子（Heat shock factor，HSF）1是热休克等应激反应的关键转录因子，通过磷酸化激活HSP家族的表达。因此，在本研究中，我们研究了热休克（HS）是否诱导CSC/CIC。我们用HS处理人肾癌细胞系ACHN，发现HS增加侧群（SP）细胞。Western blot分析和qRT-PCR显示HS增加了DNAJB 8和SOX 2的表达。使用siRNA的基因敲低实验表明，SOX 2表达和SP细胞比率的增加取决于DNAJB 8，而DNAJB 8和SOX 2的增加取决于HSF 1。此外，用哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂替西罗莫司治疗，降低了DNAJB 8和SOX 2的表达以及SP细胞的比例。总之，结果表明热休克通过激活HSF 1诱导DNAJB 8并诱导癌症干细胞样细胞。
In a previous study, we found that DNAJB8, a heat shock protein (HSP) 40 family member is expressed in kidney cancer stem‐like cells (CSC)/cancer‐initiating cells (CIC) and that it has a role in the maintenance of kidney CSC/CIC. Heat shock factor (HSF) 1 is a key transcription factor for responses to stress including heat shock, and it induces HSP family expression through activation by phosphorylation. In the present study, we therefore examined whether heat shock (HS) induces CSC/CIC. We treated the human kidney cancer cell line ACHN with HS, and found that HS increased side population (SP) cells. Western blot analysis and qRT‐PCR showed that HS increased the expression of DNAJB8 and SOX2. Gene knockdown experiments using siRNAs showed that the increase in SOX2 expression and SP cell ratio depends on DNAJB8 and that the increase in DNAJB8 and SOX2 depend on HSF1. Furthermore, treatment with a mammalian target of rapamycin (mTOR) inhibitor, temsirolimus, decreased the expression of DNAJB8 and SOX2 and the ratio of SP cells. Taken together, the results indicate that heat shock induces DNAJB8 by activation of HSF1 and induces cancer stem‐like cells.
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影响因子：
--
作者：
Saijo H;Hirohashi Y;Torigoe T;Horibe R;Takaya A;Murai A;Kubo T;Kajiwara T;Tanaka T;Shionoya Y;Yamamoto E;Maruyama R;Nakatsugawa M;Kanaseki T;Tsukahara T;Tamura Y;Sasaki Y;Tokino T;Suzuki H;Kondo T;Takahashi H;Sato N
通讯作者：
Sato N
影响因子：
3.7
作者：
Chou SD;Prince T;Gong J;Calderwood SK
通讯作者：
Calderwood SK
影响因子：
4.3
作者：
Peired AJ;Sisti A;Romagnani P
通讯作者：
Romagnani P
影响因子：
64.5
作者：
Dai, Chengkai;Whitesell, Luke;Lindquist, Susan
通讯作者：
Lindquist, Susan
影响因子：
4.8
作者：
Bussolati, Benedetta;Bruno, Stefania;Camussi, Giovanni
通讯作者：
Camussi, Giovanni