Overexpression of Phosphoserine Aminotransferase 1 (PSAT1) Predicts Poor Prognosis and Associates with Tumor Progression in Human Esophageal Squamous Cell Carcinoma

Cell Physiol Biochem. 2016;39(1):395-406. doi: 10.1159/000445633. Epub 2016 Jul 4.

Abstract

Background/aims: Phosphoserine aminotransferase 1 (PSAT1) is over-expressed in many carcinoma tissues, however little is known regarding its expression and function in esophageal carcinogenesis. This study investigated the expression of PSAT1 in human esophageal squamous cell carcinoma (ESCC) tissues to determine the relationship between PSAT1 expression and clinicopathological factors.

Methods: The expression of PSAT1 in 64 surgical resections from esophageal carcinogenesis patients was examined by quantitative RT-PCR and immunohistochemistry and the results were compared with clinicopathological factors. In vitro experiments were performed in ESCC cells overexpressing PSAT1 to measure cell viability and invasion. Tumor formation in vivowas examined by injection of tumor cells into immunocompromised mice subcutaneously.

Results: PSAT1 expression was elevated in ESCC tissues compared to normal esophageal tissues. Increased PSAT1 expression was significantly associated with stage of disease, lymph node metastasis, distant metastasis and poor prognosis. In vitro, PSAT1 overexpression promoted ESCC cell proliferation and matrigel invasion. In vivo, injection of mice with ECSS cells overexpressing PSAT1 enhanced tumor formation. Western blot analysis revealed that PSAT1 upregulated the expression and/or activity of GSK3β/Snail.

Conclusion: PSAT1 plays a crucial role in the development of ESCC and predicts poor survival. Therefore, PSAT1 may be a promising novel anticancer therapeutic target.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Progression
  • Esophageal Neoplasms / enzymology
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • HEK293 Cells
  • Humans
  • Immunohistochemistry
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Prognosis
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transaminases / genetics*
  • Transaminases / metabolism
  • Transplantation, Heterologous

Substances

  • Transaminases
  • phosphoserine aminotransferase