Overexpression of Holocarboxylase Synthetase Predicts Lymph Node Metastasis and Unfavorable Prognosis in Breast Cancer

Anticancer Res. 2020 Aug;40(8):4557-4565. doi: 10.21873/anticanres.14461.

Abstract

Background/aim: Holocarboxylase synthetase (HLCS) catalyzes the specific attachment of biotin onto biotin-dependent carboxylases (BDCs) which play important roles in intermediary metabolism. Previous studies show that BDCs are overexpressed in many cancer types. However, expression of HLCS in cancerous tissues has not been reported.

Materials and methods: Immunohistochemistry was used to investigate HLCS expression in breast tissue obtained from 65 Thai patients, and the correlation between its expression and key clinical-pathological parameters was assessed. The role of HLCS in supporting invasion was investigated in HLCS-knockdown MCF-7 cells.

Results: Overexpression of HLCS was significantly associated with metastasis of breast cancer cells to other lymph nodes but not the sentinel and axillary lymph nodes - a finding supported in cellular invasion assays using HLCS knockdown cells. Furthermore, overexpression of HLCS reduced survival time of patients with breast cancer.

Conclusion: HLCS appears to be a prognostic marker for patients with breast cancer.

Keywords: Holocarboxylase synthetase; biotin; biotin-dependent carboxylases; breast cancer; metabolism.

MeSH terms

  • Breast / pathology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Carbon-Nitrogen Ligases / genetics*
  • Cell Line, Tumor
  • Female
  • Humans
  • Lymph Nodes / pathology
  • Lymphatic Metastasis / genetics*
  • Lymphatic Metastasis / pathology
  • MCF-7 Cells
  • Prognosis

Substances

  • Carbon-Nitrogen Ligases
  • holocarboxylase synthetases
  • biotin carboxylase