Apoptosis Research Centre, National University of Ireland, Galway, Ireland; Centre de Lutte Contre le Cancer Eugène Marquis, 35000 Rennes, France.
Apoptosis Research Centre, National University of Ireland, Galway, Ireland.
Semin Cancer Biol. 2015 Aug;33:57-66. doi: 10.1016/j.semcancer.2015.03.003. Epub 2015 Mar 23.
Cancer cells are exposed to intrinsic (oncogene) or extrinsic (microenvironmental) challenges, leading to activation of stress response pathways. The unfolded protein response (UPR) is the cellular response to endoplasmic reticulum (ER) stress and plays a pivotal role in tumor development. Depending on ER stress intensity and duration, the UPR is either pro-survival to preserve ER homeostasis or pro-death if the stress cannot be resolved. On one hand, the adaptive arm of the UPR is essential for cancer cells to survive the harsh conditions they are facing, and on the other hand, cancer cells have evolved mechanisms to bypass ER stress-induced cell death, thereby conferring them with a selective advantage for malignant transformation. Therefore, the mechanisms involved in the balance between survival and death outcomes of the UPR may be exploited as therapeutic tools to treat cancer.
癌细胞会受到内在（oncogene）或外在（microenvironmental）挑战的影响，从而激活应激反应途径。未折叠蛋白反应（UPR）是细胞对内质网（ER）应激的反应，在肿瘤发生发展中起着关键作用。根据 ER 应激的强度和持续时间，UPR 要么是为了维持 ER 稳态而促进生存，要么是在应激无法解决时促进死亡。一方面，UPR 的适应性分支对于癌细胞在面临恶劣条件时的存活是必不可少的，另一方面，癌细胞已经进化出了绕过 ER 应激诱导的细胞死亡的机制，从而使它们在恶性转化方面具有选择性优势。因此，参与 UPR 生存和死亡结果之间平衡的机制可能被用作治疗癌症的治疗工具。
