Argininosuccinate lyase is a potential therapeutic target in breast cancer

Hau Lun Huang, Wei Ching Chen, Hui Ping Hsu, Chien Yu Cho, Yu Hsuan Hung, Chih Yang Wang, Ming Derg Lai

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Arginine is a non-essential amino acid that modulates nitric oxide production and cancer homeostasis. In our previous study, we observed that blocking argininosuccinate lyase (ASL) attenuates tumor progression in liver cancer. However, the role of ASL in human breast cancer has been studied to a lesser degree. In the present study, we investigated the effect of targeting ASL in breast cancer. We found that ASL was induced by ER stress and was significantly upregulated in breast cancer tissues compared to that in the corresponding normal tissues. Downregulation of ASL inhibited the growth of breast cancer in vitro and in vivo. The level of cell cyclerelated gene, cyclin A2, was reduced and was accompanied by a delay in G2/M transition. ASL shRNA-induced cell inhibition was rescued by exogenous cyclin A2. Furthermore, autophagy was observed in the cells expressing ASL shRNA, and inhibition of autophagy reduced cell growth, indicating that autophagy played a cell survival role in the ASL knockdown cells. Moreover, inhibition of ASL reduced NO content. Introduction of the NO donor partially restored the growth inhibition by ASL shRNA. Thus, the mechanism induced by ASL shRNA which occurred in human breast cancer may be attributed to a decrease in cyclin A2 and NO.

Original languageEnglish
Pages (from-to)3131-3139
Number of pages9
JournalOncology Reports
Volume34
Issue number6
DOIs
Publication statusPublished - Dec 1 2015
Externally publishedYes

Keywords

  • Argininosuccinate lyase
  • Autophagy
  • Breast cancer
  • Cyclin A
  • Endoplasmic reticulum
  • Nitric oxide

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Huang, H. L., Chen, W. C., Hsu, H. P., Cho, C. Y., Hung, Y. H., Wang, C. Y., & Lai, M. D. (2015). Argininosuccinate lyase is a potential therapeutic target in breast cancer. Oncology Reports, 34(6), 3131-3139. https://doi.org/10.3892/or.2015.4280