Similarities and Differences of Hsp70, hsc70, Grp78 and Mortalin as Cancer Biomarkers and Drug Targets.
Similarities and Differences of Hsp70, hsc70, Grp78 and Mortalin as Cancer Biomarkers and Drug Targets.
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DOI：
10.3390/cells10112996
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发表时间：
2021-11-03
期刊：
影响因子：
6
通讯作者：
Benbrook DM
中科院分区：
文献类型：
--
作者：
Rai R;Kennedy AL;Isingizwe ZR;Javadian P;Benbrook DM
背景：Heath Shock Protein 70 （HSP70）伴侣蛋白的上调支持癌细胞存活。它们的高度同源性给区分它们在实验或预防和治疗策略上带来了挑战。本研究的目的是确定分别由HSPA1、HSPA8、HSPA5和HSPA9基因编码的Hsp70家族成员Hsp70、hsc70、Grp78和Mortalin的异同。方法：采用hspaa1、HSPA5、HSPA8、HSPA9基因或蛋白名称或同义词结合生物学或癌症相关术语进行文献综述。匠心途径分析用于识别和比较直接结合个体伴侣及其相关途径的蛋白质谱。研究了TCGA数据，以确定hsc70与癌症患者生存的关系。ClinicalTrials.gov网站被用来确定HSP70家族研究。结果：两种伴侣蛋白具有相似的蛋白折叠功能。它们不同的细胞效应是由共同伴侣蛋白和客户蛋白结合它们在细胞内和细胞外的定位决定的。它们的上调与多种癌症患者预后恶化有关，并可刺激肿瘤免疫反应或耐药。它们的抑制作用选择性地杀死癌细胞而不是健康细胞。结论：Hsp70、hsc70、Grp78和mortalin的差异为针对个别癌症和联合治疗校准Hsp70抑制剂提供了机会。
Background: Upregulation of Heath Shock Protein 70 (HSP70) chaperones supports cancer cell survival. Their high homology causes a challenge to differentiate them in experimental or prevention and treatment strategies. The objective of this investigation was to determine similarities and differences of Hsp70, hsc70, Grp78 and Mortalin members of the HSP70 family encoded by HSPA1, HSPA8, HSPA5 and HSPA9 genes, respectively. Methods: Literature reviews were conducted using HSPA1, HSPA5, HSPA8 and HSPA9 gene or protein names or synonyms combined with biological or cancer-relevant terms. Ingenuity Pathway Analysis was used to identify and compare profiles of proteins that directly bind individual chaperones and their associated pathways. TCGA data was probed to identify associations of hsc70 with cancer patient survival. ClinicalTrials.gov was used to identify HSP70 family studies. Results: The chaperones have similar protein folding functions. Their different cellular effects are determined by co-chaperones and client proteins combined with their intra- and extra-cellular localizations. Their upregulation is associated with worse patient prognosis in multiple cancers and can stimulate tumor immune responses or drug resistance. Their inhibition selectively kills cancer over healthy cells. Conclusions: Differences in Hsp70, hsc70, Grp78 and mortalin provide opportunities to calibrate HSP70 inhibitors for individual cancers and combination therapies.
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影响因子：
5.2
作者：
Chandra V;Rai R;Benbrook DM
通讯作者：
Benbrook DM
Mortalin在胰腺癌中的表达及其临床和预后意义
影响因子：
3.3
作者：
Cui, Xuelian;Li, Zhenling;Jin, Aihua
通讯作者：
Jin, Aihua
DOI：
10.1083/jcb.137.4.825
发表时间：
1997-05-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Agarraberes FA;Terlecky SR;Dice JF
通讯作者：
Dice JF
影响因子：
8.8
作者：
Brehme M;Voisine C;Rolland T;Wachi S;Soper JH;Zhu Y;Orton K;Villella A;Garza D;Vidal M;Ge H;Morimoto RI
通讯作者：
Morimoto RI
DOI：
10.1083/jcb.200506074
发表时间：
2005-10-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kose S;Furuta M;Koike M;Yoneda Y;Imamoto N
通讯作者：
Imamoto N