DPP3 promotes breast cancer tumorigenesis by stabilizing FASN and promoting lipid synthesis

Acta Biochim Biophys Sin (Shanghai). 2024 May 25;56(5):805-818. doi: 10.3724/abbs.2024054.

Abstract

DPP3, a dipeptidyl peptidase, participates in a variety of pathophysiological processes. DPP3 is upregulated in cancer and might serve as a key factor in the tumorigenesis and progression of various malignancies. However, its specific role and molecular mechanism are still unknown. In this study, the expression of DPP3 in breast cancer tissues is analyzed using TCGA database. Kaplan-Meier survival analysis is performed to estimate the effect of DPP3 on the survival outcomes. To explore the biological function and mechanisms of DPP3 in breast cancer, biochemical and cell biology assays are conducted in vitro. DPP3 expresses at a higher level in breast cancer tissues than that in adjacent tissues in both TCGA database and clinical samples. Patients with high expression of DPP3 have poor survival outcomes. The proliferation and migration abilities of tumor cells with stable DPP3 knockout in breast cancer cell lines are significantly inhibited, and apoptosis is increased in vitro. GSEA analysis shows that DPP3 can affect lipid metabolism and fatty acid synthesis in tumors. Subsequent experiments show that DPP3 could stabilize FASN expression and thus promote fatty acid synthesis in tumor cells. The results of the metabolomic analysis also confirm that DPP3 can affect the content of free fatty acids. This study demonstrates that DPP3 plays a role in the reprogramming of fatty acid metabolism in tumors and is associated with poor prognosis in breast cancer patients. These findings will provide a new therapeutic target for the treatment of breast cancer.

Keywords: breast cancer; dipeptidyl peptidase 3; fatty acid synthetase.

MeSH terms

  • Apoptosis / genetics
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Carcinogenesis* / genetics
  • Carcinogenesis* / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation* / genetics
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / genetics
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / metabolism
  • Fatty Acid Synthase, Type I* / genetics
  • Fatty Acid Synthase, Type I* / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lipid Metabolism / genetics
  • MCF-7 Cells

Substances

  • Fatty Acid Synthase, Type I
  • FASN protein, human
  • DPP3 protein, human
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases

Grants and funding

This work was supported by the grant from the Natural Science Foundation of Hubei Province of China (No. 2023BCB022).