Oxysterol-Binding Protein 2 Promotes Pancreatic Ductal Adenocarcinoma Progression Through Epithelial-Mesenchymal Transition.

Shuai Huang,Jianhua Jiang,Xudong Zhang,Kai Luo,Renfeng Li,Li Jiang

doi:10.3389/fonc.2021.762233

Abstract

Oxysterol-binding protein 2 (OSBP2) is crucial for promoting the growth and development of cancers; however, its effects on pancreatic ductal adenocarcinoma (PDAC) are still unclear. Here, we report that OSBP2 is an efficient tumor-associated protein to lead to extremely malignant characteristics in PDAC. We discovered that increased OSBP2 expression in primary tumors was associated with shorter survival in PDAC patients. Therefore, we used immunohistochemistry (IHC) to analyze the levels of OSBP2 expression in PDAC tissues and adjacent paracancerous tissues. We used wound healing and Transwell assays to evaluate the effects of OSBP2 on PDAC cell (ASPC-1 and BXPC-3) migration and invasion, respectively, and CCK-8 and Annexin V/PI double staining to evaluate the effects of OSBP2 on PDAC cell proliferation and apoptosis, respectively. Western blotting was used to analyze the effect of OSBP2 on the PDAC cell phenotype. We also explored the effect of OSBP2 on chemosensitivity to gemcitabine (GEM) and 5-fluorouracil (5-FU). We validated these findings in an in vivo mouse model. The data show that OSBP2 overexpression promoted PDAC cell migration, invasion, proliferation and chemotherapy resistance, and decreased apoptosis. OSBP2 overexpression downregulated E-cadherin expression and upregulated N-cadherin, vimentin, Snail, Slug, ZEB1, and β-catenin expression. Taken together, our findings indicated that OSBP2 was overexpressed in PDAC and that upregulation of OSBP2 may promote PDAC progression. Therefore, OSBP2 may have potential diagnostic and therapeutic value in PDAC.

Highlights

Pancreatic ductal adenocarcinoma (PDAC) is a serious health problem worldwide owing to its poor prognosis, five-year survival rate of less than 5%, and ranks as the eighth most common cause of cancer-related deaths globally [1,2,3]
Our data demonstrated that Oxysterol-binding protein 2 (OSBP2) expression in PDAC tissues were related to nerve invasion (P
We further investigated the effect of OSBP2 expression on the biological behavior of PDAC cells

Summary

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is a serious health problem worldwide owing to its poor prognosis, five-year survival rate of less than 5%, and ranks as the eighth most common cause of cancer-related deaths globally [1,2,3]. In China, the median survival of PDAC patients is 7.8 months, with 30.0% of patients undergoing effective radical resection and 9.8% of patients undergoing synthetic curative treatment [4, 5]. Tremendous efforts have been made and there has been great progress in this field over the last few decades, PDAC patient survival has not exhibited obvious improvement [6, 7]. Its aggressive biological phenotype that elicits early local invasion and metastasis features causes low survival rates [8, 9]. We need to further elucidate the molecular mechanisms behind the occurrence, development, treatment resistance and metastasis of this deadly disease

Methods

Results

Conclusion