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

Int J Mol Sci. 2022 Jan 21;23(3):1176. 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.

Keywords: TRIM37; immune microenvironment; pancreatic cancer.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Movement*
  • Cell Proliferation*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Invasiveness
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Tripartite Motif Proteins / genetics
  • Tripartite Motif Proteins / metabolism*
  • Tumor Cells, Cultured
  • Tumor Microenvironment*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • Tripartite Motif Proteins
  • TRIM37 protein, human
  • Ubiquitin-Protein Ligases