Direct association of heat shock protein 20 (HSPB6) with phosphoinositide 3-kinase (PI3K) in human hepatocellular carcinoma: regulation of the PI3K activity.
Direct association of heat shock protein 20 (HSPB6) with phosphoinositide 3-kinase (PI3K) in human hepatocellular carcinoma: regulation of the PI3K activity.
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DOI：
10.1371/journal.pone.0078440
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kozawa O
中科院分区：
文献类型：
--
作者：
Matsushima-Nishiwaki R;Kumada T;Nagasawa T;Suzuki M;Yasuda E;Okuda S;Maeda A;Kaneoka Y;Toyoda H;Kozawa O
HSP20 （HSPB6）是一种小热休克蛋白（HSPs），在多种组织中组成性表达，具有多种功能。我们之前报道了HSP20在人肝细胞癌（HCC）细胞中的表达水平与HCC的进展呈负相关，并且HSP20通过AKT和丝裂原激活的蛋白激酶信号通路抑制HCC细胞的生长。然而，HSP20调控这些信号通路的确切机制仍有待阐明。为了阐明这种作用在HCC中的细节，我们利用HSP20过表达的人HCC来源的HuH7细胞探索了HSP20在HCC中的直接靶点。HuH7细胞中的HSP20蛋白与AKT的上游激酶PI3K的p85调控亚基和p110催化亚基共免疫沉淀。虽然HSP20在HCC细胞中过表达不影响PI3K的表达水平，但HSP20过表达可下调未刺激细胞甚至转化生长因子-α刺激细胞中PI3K的活性。HSP20与PI3K的关联也在人肝癌组织中被观察到。这些发现强烈提示HSP20直接与PI3K结合，抑制其在HCC中的活性，从而抑制AKT通路，从而降低HCC的生长。
HSP20 (HSPB6), one of small heat shock proteins (HSPs), is constitutively expressed in various tissues and has several functions. We previously reported that the expression levels of HSP20 in human hepatocellular carcinoma (HCC) cells inversely correlated with the progression of HCC, and that HSP20 suppresses the growth of HCC cells via the AKT and mitogen-activated protein kinase signaling pathways. However, the exact mechanism underlying the effect of HSP20 on the regulation of these signaling pathways remains to be elucidated. To clarify the details of this effect in HCC, we explored the direct targets of HSP20 in HCC using human HCC-derived HuH7 cells with HSP20 overexpression. HSP20 proteins in the HuH7 cells were coimmunoprecipitated with the p85 regulatory subunit and p110 catalytic subunit of phosphoinositide 3-kinase (PI3K), an upstream kinase of AKT. Although HSP20 overexpression in HCC cells failed to affect the expression levels of PI3K, the activity of PI3K in the unstimulated cells and even in the transforming growth factor-α stimulated cells were downregulated by HSP20 overexpression. The association of HSP20 with PI3K was also observed in human HCC tissues in vivo. These findings strongly suggest that HSP20 directly associates with PI3K and suppresses its activity in HCC, resulting in the inhibition of the AKT pathway, and subsequently decreasing the growth of HCC.
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影响因子：
20.1
作者：
Fan GC;Zhou X;Wang X;Song G;Qian J;Nicolaou P;Chen G;Ren X;Kranias EG
通讯作者：
Kranias EG
影响因子：
5
作者：
Fan GC;Kranias EG
通讯作者：
Kranias EG
DOI：
10.1152/ajplung.00235.2007
发表时间：
2008-01-01
影响因子：
4.9
作者：
Komalavilas, Padmini;Penn, Raymond B.;Brophy, Colleen M.
通讯作者：
Brophy, Colleen M.
DOI：
10.1111/j.1349-7006.2001.tb01187.x
发表时间：
2001-09
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Tanaka K;Fujimoto Y;Suzuki M;Suzuki Y;Ohtake T;Saito H;Kohgo Y
通讯作者：
Kohgo Y
磷酸肌醇3-激酶调节亚基P85Alpha可以通过阴性调节生长因子信号传导来发挥肿瘤抑制特性。
影响因子：
11.2
作者：
Taniguchi CM;Winnay J;Kondo T;Bronson RT;Guimaraes AR;Alemán JO;Luo J;Stephanopoulos G;Weissleder R;Cantley LC;Kahn CR
通讯作者：
Kahn CR