Huang Jingjing, Pan Huayang, Wang Jinge, Wang Tong, Huo Xiaoyan, Ma Yong, Lu Zhaoyang, Sun Bei, Jiang Hongchi
Department of General Surgery, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150001, People's Republic of China.
The Second Affiliated Hospital & College of Nursing, Harbin Medical University, Harbin, People's Republic of China.
Cell Biosci. 2021 Jan 29;11(1):26. doi: 10.1186/s13578-021-00538-z.
Colorectal cancer (CRC) is a gastrointestinal malignancy originating from either the colon or the rectum. A growing number of researches prove that the unfolded protein response (UPR) is closely related to the occurrence and progression of colorectal cancer. The UPR has three canonical endoplasmic reticulum (ER) transmembrane protein sensors: inositol requiring kinase 1 (IRE1), pancreatic ER eIF2α kinase (PERK), and activating transcription factor 6 (ATF6). Each of the three pathways is closely associated with CRC development. The three pathways are relatively independent as well as interrelated. Under ER stress, the activated UPR boosts the protein folding capacity to maximize cell adaptation and survival, whereas sustained or excessive ER triggers cell apoptosis conversely. The UPR involves different stages of CRC pathogenesis, promotes or hinders the progression of CRC, and will pave the way for novel therapeutic and diagnostic approaches. Meanwhile, the correlation between different signal branches in UPR and the switch between the adaptation and apoptosis pathways still need to be further investigated in the future.
结直肠癌（CRC）是一种起源于结肠或直肠的胃肠道恶性肿瘤。越来越多的研究证明，未折叠蛋白反应（UPR）与结直肠癌的发生和发展密切相关。UPR有三种典型的内质网（ER）跨膜蛋白传感器：肌醇需要激酶1（IRE1）、胰腺内质网eIF2α激酶（PERK）和激活转录因子6（ATF6）。这三条途径中的每一条都与CRC的发展密切相关。这三条途径既相对独立又相互关联。在内质网应激下，激活的UPR增强蛋白质折叠能力，以最大限度地提高细胞适应性和存活率，而持续或过度的内质网应激则相反地触发细胞凋亡。UPR涉及CRC发病机制的不同阶段，促进或阻碍CRC的进展，并将为新的治疗和诊断方法铺平道路。同时，UPR中不同信号分支之间的相关性以及适应性和凋亡途径之间的转换在未来仍需进一步研究。
