HERPUD1, a member of the Endoplasmic Reticulum Protein Quality Control Mechanism, may be a good target for suppressing tumorigenesis in Breast Cancer Cells.

INTRODUCTION: Breast cancer is the most frequently diagnosed cancer type in women, and it is the second leading cause of cancer-related death in women. Recent studies highlight the importance of the Endoplasmic reticulum (ER) protein quality control (ERQC) mechanism for the survival of many cancers and it also has been recommended as a good target for the treatment of many cancer types. Homocysteine inducible ER protein with ubiquitin-like domain 1 (HERPUD1) functions as one of the main components of ER-associated degradation (ERAD), which is an ER-resident protein quality mechanism. Today, the association of HERPUD1 with breast carcinogenesis is still not fully understood. Herein, we evaluate the possibility of HERPUD1 as a potential therapeutic target for breast cancer.
METHODS: The effect of HERPUD1 silencing on epithelial-mesenchymal transition, angiogenesis and cell cycle proteins was analyzed by immunoblotting studies. To test the role of HERPUD1 on tumorigenic features, WST-1 based cell proliferation assay, wound-healing assay, 2D colony formation assay and Boyden-Chamber invasion assay were performed in MCF-7 cells. The statistical significance of the differences between the groups was determined by Student t-test.
RESULTS: Our results showed that suppression of HERPUD1 expression led to decreased cell cycle-related protein levels including Cyclin A2, Cyclin B1 and Cyclin E1 in MCF-7 cells. Also, silencing of HERPUD1 was remarkably decreased expression levels of epithelial-mesenchymal transition-related N-cadherin and angiogenesis marker, VEGF-A. Moreover, we determined that significantly decreased the cell proliferation, migration, invasion and colony formation in HERPUD1 silenced MCF-7 cells.
DISCUSSION AND CONCLUSION: HERPUD1 may have the potential to be an effective target for biotechnological and pharmacological targeting strategies to be developed for the treatment of breast cancer.