Increased expression of glutamine transporter SNAT2/SLC38A2 promotes glutamine dependence and oxidative stress resistance, and is associated with worse prognosis in triple-negative breast cancer

Matteo Morotti, Christos E. Zois, Rokaya El-Ansari, Madeleine L. Craze, Emad A. Rakha, Shih Jung Fan, Alessandro Valli, Syed Haider, Deborah C.I. Goberdhan, Andrew R. Green, Adrian L. Harris

研究成果: 雜誌貢獻期刊論文同行評審

60 引文 斯高帕斯(Scopus)

摘要

Background: Glutamine (Gln) is an abundant nutrient used by cancer cells. Breast cancers cells and particularly triple-receptor negative breast cancer (TNBC) are reported to be dependent on Gln to produce the energy required for survival and proliferation. Despite intense research on the role of the intracellular Gln pathway, few reports have focussed on Gln transporters in breast cancer and TNBC. Methods: The role and localisation of the Gln transporter SLC38A2/SNAT2 in response to Gln deprivation or pharmacological stresses was examined in a panel of breast cancer cell lines. Subsequently, the effect of SLC38A2 knockdown in Gln-sensitive cell lines was analysed. The prognostic value of SLC38A2 in a cohort of breast cancer was determined by immunohistochemistry. Results: SLC38A2 was identified as a strongly expressed amino acid transporter in six breast cancer cell lines. We confirmed an autophagic route of degradation for SLC38A2. SLC38A2 knockdown decreased Gln consumption, inhibited cell growth, induced autophagy and led to ROS production in a subgroup of Gln-sensitive cell lines. High expression of SLC38A2 protein was associated with poor breast cancer specific survival in a large cohort of patients (p = 0.004), particularly in TNBC (p = 0.02). Conclusions: These results position SLC38A2 as a selective target for inhibiting growth of Gln-dependent breast cancer cell lines.

原文???core.languages.en_GB???
頁(從 - 到)494-505
頁數12
期刊British Journal of Cancer
124
發行號2
DOIs
出版狀態已出版 - 19 1月 2021

指紋

深入研究「Increased expression of glutamine transporter SNAT2/SLC38A2 promotes glutamine dependence and oxidative stress resistance, and is associated with worse prognosis in triple-negative breast cancer」主題。共同形成了獨特的指紋。

引用此