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

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.

Identification of Two Novel CIL-102 Upregulations of ERP29 and FUMH to Inhibit the Migration and Invasiveness of Colorectal Cancer Cells by Using the Proteomic Approach

“…By using the proteomic approach with the MALDI-TOF-TOF analysis, we wanted to investigate the novel CIL-102-upregulated protein [ 27 , 28 ]. More than 800 protein spots from cell lysates of DLD-1 cells, with or without the CIL-102 treatment, were visualized in the silver-stained 2D-PAGE analysis ( Figure 4 ).…”

“…From previous studies, one protein ERP29 was shown to be a tumor suppressor and a chaperone protein, which involves the regulation of primary tumor development and the arrest of cell growth [27]. Another differential display protein, FUMH, also shows anti-tumor functions, including the inactivation of tumor metastasis, tumor aggressiveness, and EMT changes by epigenetic modification [28]. protein spots in the CIL-102-treated group) with a three-fold difference between both groups, were subjected to a MALDI-TOF-TOF analysis.…”

Proteomic Characterization of Proliferation Inhibition of Well-Differentiated Laryngeal Squamous Cell Carcinoma Cells Under Below-Background Radiation in a Deep Underground Environment

“…As an integral chaperon protein of the ER, calnexin (CANX) promotes cancer cell growth and proliferation. Endoplasmic reticulum protein 29 (ERp29), which plays a role in protein unfolding and secretion, is associated with the ER stress response (26). Heat shock protein 5 (HSPA5/GRP78/BiP) protects cells against ER stress and damage caused by reactive oxygen species, and helps cells survive by regulating calcium signaling in mitochondriaassociated ER membranes (27).…”

Role of a genetic variation in the microRNA-4421 binding site of ERP29 regarding risk of oropharynx cancer and prognosis

“…Noteworthily, ERp29 overexpression was associated with mesenchymal-epithelial transition (MET) upregulation and epithelial morphogenesis 8 – 10 as well as with epithelial-mesenchymal transition downregulation in cancer cells 23 . In fact, ERp29 overexpression was showed to be associated with metastasis promotion in breast cancer 24 , uveal melanoma 25 , and colorectal cancer 26 . However, there are no studies focusing on the role of ERp29 in OPSCC risk or prognosis.…”