ATP synthase ecto-α-subunit: A novel therapeutic target for breast cancer

Jian Pan, Li Chao Sun, Yan Fang Tao, Zhuan Zhou, Xiao Li Du, Liang Peng, Xing Feng, Jian Wang, Yi Ping Li, Ling Liu, Shui Yan Wu, Yan Lan Zhang, Shao Yan Hu, Wen Li Zhao, Xue Ming Zhu, Guo Liang Lou*, Jian Ni

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Background: Treatment failure for breast cancer is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in breast cancer cells in vitro and in vivo. Identification of new targets will facilitate the developmental pace of new techniques in screening and early diagnosis. Improved abilities to predict progression and metastasis, therapeutic response and toxicity will help to increase survival of breast cancer patients.Methods: Differential protein expression in two breast cancer cell lines, one with high and the other with low metastatic potential, was analyzed using two-dimensional liquid phase chromatographic fractionation (Proteome Lab PF 2D system) followed by matrix-assisted laser desorption/time-of-flight mass spectrometry (MALDI-TOF/MS).Results: Up regulation of α-subunit of ATP synthase was identified in high metastatic cells compared with low metastatic cells. Immunohistochemical analysis of 168 human breast cancer specimens on tissue microarrays revealed a high frequency of ATP synthase α-subunit expression in breast cancer (94.6%) compared to normal (21.2%) and atypical hyperplasia (23%) breast tissues. Levels of ATP synthase expression levels strongly correlated with large tumor size, poor tumor differentiation and advanced tumor stages (P < 0.05). ATP synthase α-subunit over-expression was detected on the surface of a highly invasive breast cancer cell line. An antibody against the ATP synthase α-subunit inhibited proliferation, migration and invasion in these breast cancer cells but not that of a non-tumor derived breast cell line.Conclusions: Over-expression of ATP synthase α-subunit may be involved in the progression and metastasis of breast cancer, perhaps representing a potential biomarker for diagnosis, prognosis and a therapeutic target for breast cancer. This finding of this study will help us to better understand the molecular mechanism of tumor metastasis and to improve the screening, diagnosis, as well as prognosis and/or prediction of responses to therapy for breast cancer.

Original languageEnglish (US)
Article number211
JournalJournal of Translational Medicine
Volume9
Issue number1
DOIs
StatePublished - Dec 8 2011

Keywords

  • Atp synthase α-subunit
  • Breast cancer
  • Monoclonal antibody
  • Tissue microarray
  • Two-dimensional liquid phase chromatographic fractionation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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