Sushi Repeat Containing Protein X-linked 2 Is a Downstream Signal of LEM Domain Containing 1 and Acts as a Tumor-Promoting Factor in Oral Squamous Cell Carcinoma

Int J Mol Sci. 2020 May 22;21(10):3655. doi: 10.3390/ijms21103655.

Abstract

Because oral squamous cell carcinomas (OSCCs) have a high potential for locoregional invasion and nodal metastasis, early detection and treatment are essential. A LAP2, emerin, MAN1 (LEM) domain containing 1 (LEMD1) is associated with local progression, clinical stage, nodal metastasis, poor prognosis, angiogenesis, and lymphangiogenesis in OSCC. Although LEMD is a cancer-testis antigen, the cancer-related signals related to LEMD1 remain unknown. In this study, we used a microarray analysis of OSCC cells to identify sushi repeat containing protein X-linked 2 (SRPX2) as a LEMD1-related downstream signal. LEMD1 expression was correlated with lymph node metastasis of OSCC according to the immunohistochemistry analysis. Furthermore, patients expressing SRPX2 had a significantly worse prognosis than those without SRPX2 expression. The concentration of SRPX2 in OSCC was positively correlated with the concentrations of LEMD1, urokinase plasminogen activator receptor (uPAR), and hepatocyte growth factor (HGF). In OSCC cells, SRPX2 secretion levels were elevated by interactions with uPAR and HGF. We also found that SRPX2 promotes endothelial cell proliferation and adhesion between endothelial cells and OSCC cells. These results suggest that SRPX2 might be a useful tumor marker for OSCC.

Keywords: angiogenesis; chemosensitivity; lymphangiogenesis; metastasis; oral cancer; sushi repeat containing protein X-linked 2.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / secondary
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Drug Resistance, Neoplasm / genetics
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Lymphatic Metastasis*
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / mortality
  • Mouth Neoplasms / pathology
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neovascularization, Pathologic / genetics
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • RNA, Small Interfering
  • Receptors, Urokinase Plasminogen Activator / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics

Substances

  • HGF protein, human
  • LEMD1 protein, human
  • Membrane Proteins
  • Neoplasm Proteins
  • RNA, Small Interfering
  • Receptors, Urokinase Plasminogen Activator
  • SRPX2 protein, human
  • Hepatocyte Growth Factor