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GLYAT suppresses liver cancer and clear cell renal cell carcinoma progression by downregulating ROCK1 expression

Yechen Xia1, Wentao Huang2, Guang-Zhi Jin1

  • 1Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Translational Cancer Research
|October 21, 2024
PubMed
Abstract

Insights

Glycine-N-acyltransferase (GLYAT) is downregulated in liver cancer and clear cell renal cell carcinoma (ccRCC), acting as a tumor suppressor. Its reduced expression indicates a poor prognosis, and it inhibits cancer progression by downregulating ROCK1.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The liver and kidney are vital metabolic organs and common sites for tumor development.
  • Glycine-N-acyltransferase (GLYAT) is predominantly expressed in the liver and kidney but shows reduced levels in various tumors.
  • The precise roles and molecular mechanisms of GLYAT in liver cancer and clear cell renal cell carcinoma (ccRCC) remain incompletely understood.

Purpose of the Study:

  • To investigate the expression patterns and clinical significance of GLYAT in liver cancer and ccRCC.
  • To elucidate the functional role and molecular mechanisms of GLYAT in the progression of liver cancer and ccRCC.

Main Methods:

  • Proteomics was employed to identify differentially expressed proteins in liver cancer.
  • Western blot and immunohistochemistry (IHC) were utilized to analyze GLYAT protein expression.
  • Cellular assays and xenograft models in nude mice were performed to assess GLYAT's function and downstream targets.

Main Results:

  • GLYAT was found to be lowly expressed in both liver cancer and ccRCC tissues.
  • Low GLYAT expression correlated with poor prognosis in patients with liver cancer and ccRCC.
  • Overexpression of GLYAT inhibited cancer cell proliferation and migration, while GLYAT downregulation promoted these processes. GLYAT was identified to downregulate Rho-associated coiled-coil-containing protein kinase 1 (ROCK1).

Conclusions:

  • GLYAT is significantly downregulated in liver cancer and ccRCC, serving as a prognostic biomarker.
  • GLYAT functions as a tumor suppressor by inhibiting cancer progression, specifically through the downregulation of ROCK1.
Keywords:
Liver cancerRho-associated coiled-coil-containing protein kinase 1 (ROCK1)clear cell renal cell carcinoma (ccRCC)glycine-N-acyltransferase (GLYAT)prognostic markers

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