Tumour cells endure both oncogenic and environmental stresses during cancer progression. Transformed cells must meet increased demands for protein and lipid production needed for rapid proliferation and must adapt to exist in an oxygen‐ and nutrient‐deprived environment. To overcome such challenges, cancer cells exploit intrinsic adaptive mechanisms such as the unfolded protein response (UPR). The UPR is a pro‐survival mechanism triggered by accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER), a condition referred to as ER stress. IRE1, PERK and ATF6 are three ER anchored transmembrane receptors. Upon induction of ER stress, they signal in a coordinated fashion to re‐establish ER homoeostasis, thus aiding cell survival. Over the past decade, evidence has emerged supporting a role for the UPR in the establishment and progression of several cancers, including breast cancer, prostate cancer and glioblastoma multiforme. This review discusses our current knowledge of the UPR during oncogenesis, tumour growth, metastasis and chemoresistance.

中文翻译：

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未折叠蛋白反应在癌症进展中的作用：从肿瘤发生到化学抗性

肿瘤细胞在癌症进展过程中承受致癌和环境压力。转化的细胞必须满足快速增殖所需的蛋白质和脂质生产不断增加的需求，并且必须适应存在于缺氧和营养缺乏的环境中。为了克服这些挑战，癌细胞利用内在的适应性机制，如未折叠蛋白反应 (UPR)。UPR 是一种促生存机制，由内质网 (ER) 中未折叠或错误折叠蛋白质的积累触发，这种情况称为 ER 应激。IRE1、PERK 和 ATF6 是三种内质网锚定跨膜受体。在诱导内质网应激后，它们以协调的方式发出信号以重建内质网稳态，从而帮助细胞存活。在过去的十年，已经出现的证据支持普遍定期审议在多种癌症的建立和发展中的作用，包括乳腺癌、前列腺癌和多形性胶质母细胞瘤。本综述讨论了我们目前对 UPR 在肿瘤发生、肿瘤生长、转移和化学耐药性过程中的知识。