GRP78在肿瘤发生发展及化疗耐药中的作用

Critical roles of GRP78 in carcinogenesis, growth and chemoresistance of malignancy

葡萄糖调节蛋白78（GRP78）作为内质网重要的分子伴侣，可被各种肿瘤微环境变化（如低糖、低氧等）诱导呈高表达。GRP78对肿瘤细胞增殖、凋亡、侵袭和转移以及血管形成至关重要。肿瘤组织中GRP78的表达与肿瘤的分期、分级以及预后等密切相关，并且其表达与肿瘤化疗耐药相关，而敲除GRP78可提高肿瘤对化疗药物的敏感性。GRP78不仅是预测肿瘤预后及对治疗反应的良好生物学标志物，针对肿瘤治疗普遍存在的化疗耐药，其有可能成为更具选择性的化疗靶点。

GRP78, as endoplasmic reticulum resident chaperone, is highly induced by a variety of tumor microenvimnmental stresses, such as hypoxia and glucose deprivation. GRP78 is implicated in tumor cell proliferation, apoptosis, invasion, metastasis and angiogenesis. Recent evidence indicates that GRP78 levels is correlated with pathological grade, stage and prognosis for the majority of solid tumors. In addition, GRP78 plays an important role in drug tolerance and knockdown of GRP78 has been shown to sensitize malignant ceils. GRP78 could not only be a good biomarker to predict cancer progression and chemo-responsiveness, but also an appealing target for the development of a more selective chemotherapy.