Overexpression of RAB27A in Oral Squamous Cell Carcinoma Promotes Tumor Migration and Invasion via Modulation of EGFR Membrane Stability

Int J Mol Sci. 2023 Aug 23;24(17):13103. doi: 10.3390/ijms241713103.

Abstract

Oral squamous cell carcinoma (OSCC) is the most prevalent subtype of head and neck tumors, highly prone to lymph node metastasis. This study aims to examine the expression pattern of Ras-related protein Rab-27A (RAB27A) and explore its potential implications in OSCC. The expression of RAB27A was assessed through immunohistochemical analysis utilizing tissue microarrays. In vitro experiments were conducted using RAB27A-knockdown cells to investigate its impact on OSCC tumor cells. Additionally, transcriptome sequencing was performed to elucidate potential underlying mechanisms. RAB27A was significantly overexpressed in OSCC, and particularly in metastatic lymph nodes. It was positively correlated with the clinical progression and poor survival prognosis. Silencing RAB27A notably decreased the proliferation, migration, and invasion abilities of OSCC cells in vitro. A Gene Ontology (GO) enrichment analysis indicated a strong association between RAB27A and the epidermal growth factor receptor (EGFR) signaling pathway. Further investigations revealed that RAB27A regulated the palmitoylation of EGFR via zinc finger DHHC-type containing 13 (ZDHHC13). These findings provide insights into OSCC progression and highlight RAB27A as a potential therapeutic target for combating this aggressive cancer.

Keywords: EGFR; RAB27A; metastasis; oral squamous cell carcinoma; palmitoylation.

MeSH terms

  • Carcinoma, Squamous Cell* / genetics
  • ErbB Receptors / genetics
  • Head and Neck Neoplasms*
  • Humans
  • Mouth Neoplasms* / genetics
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • rab27 GTP-Binding Proteins

Substances

  • ErbB Receptors
  • RAB27A protein, human
  • rab27 GTP-Binding Proteins
  • EGFR protein, human