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

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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 - 2015 Dec 1

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Argininosuccinate Lyase
Breast Neoplasms
Cyclin A2
Small Interfering RNA
Autophagy
Therapeutics
Growth
Liver Neoplasms
Arginine

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Huang, Hau Lun ; Chen, Wei Ching ; Hsu, Hui-Ping ; Cho, Chien Yu ; Hung, Yu Hsuan ; Wang, Chih Yang ; Lai, Ming-Derg. / Argininosuccinate lyase is a potential therapeutic target in breast cancer. In: Oncology Reports. 2015 ; Vol. 34, No. 6. pp. 3131-3139.
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Argininosuccinate lyase is a potential therapeutic target in breast cancer. / Huang, Hau Lun; Chen, Wei Ching; Hsu, Hui-Ping; Cho, Chien Yu; Hung, Yu Hsuan; Wang, Chih Yang; Lai, Ming-Derg.

In: Oncology Reports, Vol. 34, No. 6, 01.12.2015, p. 3131-3139.

Research output: Contribution to journalArticle

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