TRIM37 Promotes Pancreatic Cancer Progression through Modulation of Cell Growth, Migration, Invasion, and Tumor Immune Microenvironment.

Hui-Chen Chen,Chun-Chieh Yeh,Tuyen Thi Do,Guo-Wei Wu,Chia-Chen Hsu,Hung-Chih Chang

doi:10.3390/ijms23031176

Abstract

TRIM37 dysregulation has been observed in several cancer types, implicating its possible role in tumorigenesis. However, the role of TRIM37 in pancreatic cancer progression remains unclear. In the present study, we observed that TRIM37 knockdown resulted in reduced proliferation, clonogenicity, migration, and invasion ability of pancreatic cancer cells. Furthermore, an in vivo study using an orthotopic syngeneic animal model further confirmed that reduced expression of TRIM37 in cancer cells suppressed tumor growth in vivo. Moreover, in mice bearing TRIM37 knockdown pancreatic cancer cells, the proportion of CD11b+F4/80+MHCIIlow immunosuppressive macrophages was significantly reduced in tumor milieu, which might be due to the regulatory role of TRIM37 in cytokine production by pancreatic cancer cells. Collectively, these findings suggest a key role of TRIM37 in promoting pancreatic cancer progression.

Highlights

Introduction iationsPancreatic cancer is the fourth leading cause of mortality in Western countries and has been predicted to become the second leading cause of cancer-related deaths in a decade [1].Pancreatic ductal adenocarcinoma (PDAC) stems from the exocrine pancreas and accounts for 95% of pancreatic cancers [2]
To investigate the functional role of Tripartite motif-containing 37 (TRIM37) in pancreatic cancer, the mouse pancreatic cancer cell line, Pan18-GFP-Luc (Pan18), and human pancreatic cancer cell lines, BxPC-3 and PANC-1, were infected with lentivirus bearing shTRIM37 plasmid to knockdown the expression of TRIM37
The protein expression of TRIM37 in pancreatic cancer cell lines was detected by western blotting

Summary

Introduction

Pancreatic cancer is the fourth leading cause of mortality in Western countries and has been predicted to become the second leading cause of cancer-related deaths in a decade [1]. Pancreatic ductal adenocarcinoma (PDAC) stems from the exocrine pancreas and accounts for 95% of pancreatic cancers [2]. KRAS is one of the most frequently mutated oncogenes in PDAC, colorectal cancer, and non-small cell lung cancer [3]. The five-year survival rate of patients with pancreatic cancer is lower than 4% [4]. The immune system plays a critical role in the pathogenesis of pancreatic cancer. Previous studies have shown that only KRAS mutations are not sufficient for the development of PDAC in rodents [5,6].

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