4.3 Article

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

Journal

ANTICANCER RESEARCH
Volume 40, Issue 8, Pages 4557-4565

Publisher

INT INST ANTICANCER RESEARCH
DOI: 10.21873/anticanres.14461

Keywords

Holocarboxylase synthetase; biotin-dependent carboxylases; biotin; breast cancer; metabolism

Categories

Funding

  1. Thailand Research Fund (TRF) [IRN59W0003]
  2. IRN-CMD
  3. Newton Advanced Fellowship through TRF [DBG60800003]
  4. Royal Society [NA160153]
  5. National Health and Medical Research Council of Australia [GN1147538]
  6. Science Achievement Scholarship

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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.

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