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Cell Journal، جلد ۲۵، شماره ۷، صفحات ۴۷۰-۴۸۲

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عنوان انگلیسی ERMP1 Facilitates The Malignant Characteristics of Colorectal Cancer Cells through Modulating PI3K/AKT/β-Catenin Pathway and Localization of GRP78
چکیده انگلیسی مقاله Objective: Endoplasmic reticulum-metallopeptidase 1 (ERMP1) is involved in cellular response to oxidative stress.
However, its functional role in proliferation and progression of cancer cells remains unknown. The focus of this study
was to investigate the molecular-mechanisms in which ERMP1 modulates the proliferation and progression of colorectal
cancer (CRC) cells under normal and environment stress conditions.
Materials and Methods: In this experimental study, ERMP1 expression was evaluated using reverse transcriptionquantitative
polymerase chain reaction (RT-qPCR) in CRC cells. ERMP1 was knocked down using lentiviral transduction
of ERMP1-specific shRNA into HCT116 cells. ERMP1 was also upregulated using lipofectamine transfection of
ERMP1-overexpressing vector into SW48 cells. To evaluate the role of ERMP1 in the cellular and environmental stress
conditions, ERMP1-downregulated cells were exposed to stressful conditions including starvation, serum free medium,
and treatment with redox or chemotherapy agents for 72 hours. The expression of AKT, p-AKT, phospho-mammalian
target of rapamycin (p-mTOR), β-catenin, p-β-catenin, E-cadherin, and Glucose-regulating protein 78 (GRP78) proteins
was evaluated by western blotting. The expression of ERMP1, CYCLIN D, and c-MYC was evaluated by RT-qPCR. The
cell surface localization of GRP78, cell cycle distribution, and apoptosis were determined by Flow cytometry.
Results: ERMP1 knock-down reduced the cellular proliferation, inactivated the PI3K/AKT pathway, prompted the
G1 arrest, and attenuated the free β-catenin and CYCLIN D expression. Opposite results were obtained in ERMP1-
overexpressed cells. Knock-down of ERMP1 also reduced the GRP78 localization at the cell surface. Various
environmental stress conditions differently affected the ERMP1-downregulated cells.
Conclusion: ERMP1 functioned as an oncogene in CRC cells by promoting malignant characteristics. The
phosphoinositide 3-kinases (PI3K)/AKT/β-catenin pathway and localization of GRP78 were closely related to the effects
of ERMP1. Consequently, ERMP1 might be regarded as a promising target in therapeutic strategies related to CRC.
کلیدواژه‌های انگلیسی مقاله β-Catenin, Colorectal cancer, ERMP1, Grp78, PI3K/AKT

نویسندگان مقاله Nasim Rahmani-Kukia |
Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

Mozhdeh Zamani |
Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

Pooneh Mokaram |
Autophagy Research Center, Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran


نشانی اینترنتی https://www.celljournal.org/article_704969_ff88215092425d09223384711b9f57b0.pdf
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