Glutamine (gln) metabolism has emerged as a cancer therapeutic target in past few years, however, the effect of gln-deprivation of bCSCs remains elusive in breast cancer. In this study, effect of glutamine on stemness and differentiation potential of bCSCs isolated from MCF-7 and MDAMB-231 were studied. We have shown that bCSCs differentiate into CD24+ epithelial population under gln-deprivation and demonstrated increased expression of epithelial markers such as e-cadherin, claudin-1 and decreased expression of mesenchymal protein n-cadherin. MCF-7-bCSCs showed a decrease in EpCAMhigh population whereas MDAMB-231-bCSCs increased CD44high population in response to gln-deprivation. The expression of intracellular stem cell markers such sox-2, oct-4 and nanog showed a drastic decrease in gene expression under gln-deprived MDAMB-231-bCSCs. Finally, localization of β-catenin in MCF-7 and MDAMB-231 cells showed its accumulation in cytosol or perinuclear space reducing its efficiency to transcribe downstream genes. Conclusively, our study demonstrated that gln-deprivation induces differentiation of bCSCs into epithelial subtypes and also reduces stemness of bCSCs mediated by reduced nuclear localization of β-catenin. It also suggests that basal and luminal bCSCs respond differentially towards changes in extracellular and intracellular gln. This study could significantly affect the gln targeting regimen of breast cancer therapeutics.
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Mrs. Monika Seervi for their technical support for flow cytometry experiments.
National Institute of Pharmaceuticals Education and Research-Ahmedabad, Department of Pharmaceutics, Ministry of Chemicals and Fertilizers, Government of India. DST-SERB Grant (ECR/2016/002038), DBT supported Ramalingaswami Grant (BT/HRD/35/02/2006).
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Jariyal, H., Gupta, C., Andhale, S. et al. Comparative stemness and differentiation of luminal and basal breast cancer stem cell type under glutamine‐deprivation. J. Cell Commun. Signal. 15, 207–222 (2021). https://doi.org/10.1007/s12079-020-00603-1
- Breast cancer stem cells
- 2‐Diazo‐norleucine (DON)
- Epithelial mesenchymal transition