Gynecologic Oncology Section, Obstetrics and Gynecology Department, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Pathology Department, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Cells. 2021 Nov 3;10(11):2996. doi: 10.3390/cells10112996.
: 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 , , and genes, respectively. Literature reviews were conducted using , , and 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. 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. Differences in Hsp70, hsc70, Grp78 and mortalin provide opportunities to calibrate HSP70 inhibitors for individual cancers and combination therapies.
热休克蛋白 70（HSP70）伴侣蛋白的上调支持癌细胞存活。它们的高度同源性导致在实验或预防和治疗策略中区分它们具有挑战性。本研究的目的是确定 HSP70 家族的 Hsp70、hsc70、Grp78 和 Mortalin 成员，分别由 、 、 和 基因编码的相似性和差异。使用 、 、 和 基因或蛋白质名称或同义词与生物或癌症相关术语结合，进行文献综述。使用 ingenuity pathway analysis 来识别和比较直接结合单个伴侣蛋白及其相关途径的蛋白图谱。TCGA 数据被探测以识别 hsc70 与癌症患者生存的关联。ClinicalTrials.gov 用于识别 HSP70 家族研究。伴侣蛋白具有相似的蛋白折叠功能。它们不同的细胞效应由共伴侣蛋白和客户蛋白以及它们的细胞内和细胞外定位决定。它们的上调与多种癌症中患者预后较差相关，并可刺激肿瘤免疫反应或耐药性。它们的抑制选择性杀死癌细胞而不影响健康细胞。Hsp70、hsc70、Grp78 和 Mortalin 的差异为针对个体癌症和联合治疗方案校准 HSP70 抑制剂提供了机会。
