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内质网应激介导的恶性抑制作用被 ERp29 抵消,并促进结直肠癌的转移。

ERp29 counteracts the suppression of malignancy mediated by endoplasmic reticulum stress and promotes the metastasis of colorectal cancer.

机构信息

Department of Pathology, Nanfang Hospital and School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

Department of Pathology and Laboratory Medicine, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China.

出版信息

Oncol Rep. 2019 Mar;41(3):1603-1615. doi: 10.3892/or.2018.6943. Epub 2018 Dec 19.

Abstract

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.

摘要

内质网蛋白 29(ERp29)是一种内质网(ER)蛋白,参与内质网应激(ERS),但关于 ERp29 与癌症疾病转移和预后中 ERS 的关联知之甚少。本研究揭示了 ERp29 对 ERS 很重要,并干扰了结直肠癌(CRC)的恶性行为。在体外和动物模型中的实验表明,ERS 抑制 CRC 细胞的生长并抑制其转移能力,但 ERp29 抵消了这些作用。此外,还证明 ERp29 恢复了 ERS 抑制的 CRC 细胞的迁移和转移行为,仅在与 Cullin5(CUL5)结合时才会如此。ERp29 还依赖 CUL5 来促进上皮-间充质转化。从 CRC 组织的免疫组化检查中发现,高表达 ERp29 预示着 457 例 CRC 病例的预后不良。对 CRC 患者的临床病理数据的回顾性分析与体外和体内实验的结果一致。因此,ERp29 保护 CRC 细胞免受 ERS 介导的恶性降低,以促进转移,并且可能是 CRC 治疗中医学干预的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5306/6365697/5cf72baa14bf/OR-41-03-1603-g00.jpg

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