Programmed Cell Death Protein 10 (PDCD10) Regulates Vesicle Trafficking and Contributes to the Progression of Clear Cell Renal Cell Carcinoma

J Extracell Vesicles. 2025 Jun;14(6):e70108. doi: 10.1002/jev2.70108.

Abstract

Vesicle trafficking is an essential cellular process that plays an important role in tumour progression. Here, we performed a comprehensive transcriptomic and proteomic analysis on 50 clear cell renal cell carcinoma (ccRCC) tumour samples, and the data systematically depicted the alterations in the molecular landscape. Intriguingly, our investigation uncovered profound dysregulation of the vesicle trafficking process. Particularly, PDCD10 was overexpressed in ccRCC, and functional assays showed that PDCD10 promoted cell proliferation, migration and invasion in vitro and enhanced tumour growth in vivo. Additionally, we identified PDCD10 as a critical regulator of endocytosis and exosome secretion. Proteomic analysis of extracellular vesicles (EVs) suggested that PDCD10 overexpression altered the cargo content in EVs and elevated the abundances of cell adhesion and extracellular matrix molecules. Furthermore, Erlotinib treatment impaired PDCD10-induced endocytosis and suppressed cell proliferation and invasion. Collectively, our findings underscore the significance of PDCD10 as a regulator of vesicle trafficking in ccRCC and a potential target for developing novel anticancer therapeutics.

Keywords: PDCD10; extracellular vesicles; proteomics; renal cell carcinoma; vesicle trafficking.

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins* / genetics
  • Apoptosis Regulatory Proteins* / metabolism
  • Carcinoma, Renal Cell* / genetics
  • Carcinoma, Renal Cell* / metabolism
  • Carcinoma, Renal Cell* / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Endocytosis
  • Exosomes / metabolism
  • Extracellular Vesicles* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney Neoplasms* / genetics
  • Kidney Neoplasms* / metabolism
  • Kidney Neoplasms* / pathology
  • Membrane Proteins* / genetics
  • Membrane Proteins* / metabolism
  • Mice
  • Proteomics / methods
  • Proto-Oncogene Proteins

Substances

  • Apoptosis Regulatory Proteins
  • Membrane Proteins
  • PDCD10 protein, human
  • Proto-Oncogene Proteins