Open AccessComparative stemness and differentiation of luminal and basal breast cancer stem cell type under glutamine‐deprivation
Author(s) -
Jariyal Heena,
Gupta Chanchal,
Andhale Shambhavi,
Gadge Sonali,
Srivastava Akshay
Publication year - 2021
Publication title -
journal of cell communication and signaling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 44
eISSN - 1873-961X
pISSN - 1873-9601
DOI - 10.1007/s12079-020-00603-1
Subject(s) - stem cell , population , cancer stem cell , homeobox protein nanog , microbiology and biotechnology , biology , cancer research , medicine , induced pluripotent stem cell , embryonic stem cell , biochemistry , gene , environmental health
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 EpCAM high population whereas MDAMB‐231‐bCSCs increased CD44 high 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.