ERp29 counteracts the suppression of malignancy mediated by endoplasmic reticulum stress and promotes the metastasis of colorectal cancer
ERp29 counteracts the suppression of malignancy mediated by endoplasmic reticulum stress and promotes the metastasis of colorectal cancer
复制标题
ERp29对抗内质网应激介导的恶性肿瘤抑制并促进结直肠癌转移
DOI：
10.3892/or.2018.6943
复制
发表时间：
2019-03-01
期刊：
影响因子：
4.2
通讯作者：
Deng, Yongjian
中科院分区：
文献类型：
--
作者：
Guo, Lili;Ma, Lili;Deng, Yongjian
内质网蛋白29（endoplasmic reticulum protein 29，ERp 29）是一种内质网蛋白，参与内质网应激（ER stress，ERS），但ERp 29与ERS在肿瘤转移和预后中的关系尚不清楚。本研究提示ERp 29在ERS中起重要作用，并参与大肠癌的恶性行为。体外实验和动物模型实验表明，ERS能抑制大肠癌细胞的生长和转移能力，而ERp 29能抵消ERS的这些作用。ERp 29与cullin 5（CUL 5）结合后，可恢复ERS抑制的CRC细胞的迁移和转移行为。ERp 29还依赖于CUL 5来促进上皮-间质转化。457例结直肠癌组织中ERp 29的高表达提示预后不良。对CRC患者临床病理资料的回顾性分析与体外和体内实验的结果一致。因此，ERp 29保护CRC细胞免于ERS介导的恶性肿瘤减少以促进转移，并且可能是CRC治疗的医学干预的潜在靶点。
Endoplasmic reticulum protein 29 (ERp29), an endoplasmic reticulum (ER) protein, participates in ER stress (ERS), but little is known about the association of ERp29 with ERS in the metastasis and prognosis of cancerous diseases. The present study revealed that ERp29 was important to ERS and interfered with the malignant behaviors of colorectal cancer (CRC). Experiments in in vitro and in animal models revealed that ERS inhibited the cell growth and suppressed the metastatic capacity of CRC cells, but ERp29 counteracted these effects. Furthermore, it was demonstrated that ERp29 recovered the migration and metastatic behaviors of CRC cells suppressed by ERS, mediated only when it combined with cullin5 (CUL5). ERp29 also relied on CUL5 to promote epithelial-mesenchymal transition. From the immunohistochemical examination of CRC tissues, the high expression of ERp29 was revealed to predict the poor prognosis of 457 CRC cases. The retrospective analysis of the clinicopathological data of patients with CRC was consistent with the results of the in vitro and in vivo experiments. Thus, ERp29 protected CRC cells from ERS-mediated reduction of malignancy to promote metastasis and may be a potential target of medical intervention for CRC therapy.