The Molecular Chaperone GRP78/BiP in the Development of Chemoresistance: Mechanism and Possible Treatment.

The Molecular Chaperone GRP78/BiP in the Development of Chemoresistance: Mechanism and Possible Treatment.
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DOI:
10.3389/fphar.2013.00010
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发表时间:
2013
影响因子:
5.6
通讯作者:
Maddalo D
Maddalo D
中科院分区:
医学2区
文献类型:
--
作者:
Roller C;Maddalo D

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过去几十年来,肺癌、乳腺癌、前列腺癌和胰腺癌等多种癌症的治疗取得了显着进展。然而,在最初的反应之后,肿瘤最终对化疗产生了耐药性。这种现象被称为化学耐药性,是导致大多数癌症患者死亡的原因。对治疗难治性患者的几项研究表明,分子伴侣 GRP78/结合蛋白 BiP (BiP) 在 RNA 和蛋白质表达水平上均上调。此外,GRP78/BiP 在恶性细胞中重新定位到细胞膜,但在良性细胞中则不然。在本次通讯中,我们回顾了 GRP78/BiP 在癌细胞化学耐药性发展过程中的作用和作用机制的研究。此外,我们还讨论了 GRP78 作为生物标志物和癌症治疗靶点的可能作用。
Treatment of several types of cancer such as lung, breast, prostate, and pancreas has shown notable progresses in the past decades. However, after an initial response, tumors eventually became resistant to chemotherapy. This phenomenon, known as chemoresistance, accounts for the death of most cancer patients. Several studies in patients refractory to therapy have revealed the upregulation of the molecular chaperone GRP78/Binding Protein, BiP (BiP) both at the RNA and protein expression level. Furthermore GRP78/BiP relocates to the cell membrane in malignant but not in benign cells. In this communication we review studies on the role and the mechanism of action of GRP78/BiP during development of chemoresistance in cancer cells. In addition we discuss the possible role of GRP78 as a biomarker and as a target in cancer therapy.
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