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GRP78 and next generation cancer hallmarks: An underexplored molecular target in cancer chemoprevention research.
Biochimie ( IF 3.3 ) Pub Date : 2020-05-16 , DOI: 10.1016/j.biochi.2020.05.005 Shenbagam Madhavan 1 , Sangeetha Nagarajan 2
Biochimie ( IF 3.3 ) Pub Date : 2020-05-16 , DOI: 10.1016/j.biochi.2020.05.005 Shenbagam Madhavan 1 , Sangeetha Nagarajan 2
Affiliation
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Glucose regulated protein 78 (GRP 78), a master regulator of endoplasmic reticulum stress has been reported to be up regulated in various cancers and remains a crucial link between tumor glycolysis and tumor microenvironment. Overexpressed GRP78 has also shown to induce immune suppressive molecules and thereby tumor immune evasion. On the other hand emerging reports indicates that the next generation hallmarks viz., metabolic reprogramming and immune evasion, the two distinct processes are suggested to be fundamentally linked which is yet to be explored. Our concern is, if GRP78 is considered as a connecting link between these two different processes then targeting this triangle would be a promising approach in anticancer drug discovery. Lack of sufficient literature on this aspect represents GRP78 as an under explored target in anti-cancer research. The objective of this review is to provide a concise and integrated information on GRP78 and its association with tumor glycolysis and immune evasion which will revive and draw attention of the researchers to consider GRP78 as a potential drug target for cancer intervention and it also highlights few potential natural products investigated so far as GRP78 inhibitors.
中文翻译：
GRP78和下一代癌症的标志：癌症化学预防研究中尚未开发的分子靶标。
据报道，葡萄糖调节蛋白78（GRP 78）是内质网应激的主要调节因子，在多种癌症中均被上调，并且仍然是肿瘤糖酵解与肿瘤微环境之间的关键环节。过表达的GRP78还显示出诱导免疫抑制分子，从而逃避肿瘤免疫。另一方面，新出现的报道表明，下一代标志，即代谢重编程和免疫逃逸，建议将两个不同的过程从根本上联系起来，尚待探索。我们担心的是，如果将GRP78视为这两个不同过程之间的连接环节，那么针对该三角形的靶向将是抗癌药物发现中的一种有前途的方法。在这方面缺乏足够的文献表明，GRP78是抗癌研究中尚未探索的目标。这篇综述的目的是提供有关GRP78及其与肿瘤糖酵解和免疫逃逸的关系的简明综合信息，这将使研究人员重新考虑将GRP78视为潜在的癌症干预药物靶标，这也将引起人们的注意，并重提了这一点。到目前为止，已研究了天然产物作为GRP78抑制剂。
更新日期：2020-05-16
中文翻译：
GRP78和下一代癌症的标志：癌症化学预防研究中尚未开发的分子靶标。
据报道，葡萄糖调节蛋白78（GRP 78）是内质网应激的主要调节因子，在多种癌症中均被上调，并且仍然是肿瘤糖酵解与肿瘤微环境之间的关键环节。过表达的GRP78还显示出诱导免疫抑制分子，从而逃避肿瘤免疫。另一方面，新出现的报道表明，下一代标志，即代谢重编程和免疫逃逸，建议将两个不同的过程从根本上联系起来，尚待探索。我们担心的是，如果将GRP78视为这两个不同过程之间的连接环节，那么针对该三角形的靶向将是抗癌药物发现中的一种有前途的方法。在这方面缺乏足够的文献表明，GRP78是抗癌研究中尚未探索的目标。这篇综述的目的是提供有关GRP78及其与肿瘤糖酵解和免疫逃逸的关系的简明综合信息，这将使研究人员重新考虑将GRP78视为潜在的癌症干预药物靶标，这也将引起人们的注意，并重提了这一点。到目前为止，已研究了天然产物作为GRP78抑制剂。
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