Comparative stemness and differentiation of luminal and basal breast cancer stem cell type under glutamine‐deprivation

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.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12079-020-00603-1.     

On the role of p53 in the cellular response to aneuploidy

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Insecticidal activities of two fig tree leaf extracts against the cotton pest Spodoptera litura (Fab.) and their impact on the non-target red worm Eisenia foetida (Savigny)

Extracts of botanical origin naturally contain a complex mixture of chemicals considered effective in managing lepidopteran pests. Chemical screening of the ethanolic leaf extracts of two fig tree species, Ficus lyrata and Ficus auriculata, delivered 12 and 15 phyto-compounds with relatively high peak area percentages in phytol and flavone, respectively. Larvicidal activity against Spodoptera litura yielded higher mortality rates at maximum-concentration treatment (600 ppm) with Ficus lyrata (91.3%) and Ficus auriculata (98.5%) extracts during the second instar. Sub-lethal dosages (300 ppm) of both Ficus lyrata and Ficus auriculata extracts impeded the development and reproduction of lepidopteran pests. The enzyme-inhibition activity of both fig extracts elicited a significant reduction in the major digestive enzymes alkaline phosphatase, acid phosphatase, and lactate dehydrogenase dose-responsively. Mid-gut histological screening of Ficus lyrata and Ficus auriculata extracts displayed gut lumen disruptions, shape alterations of columnar cells, and brush-border membrane damage. Further, the non-target toxicity of fig extracts against the red worm Eisenia foetida was minimal compared with that of the chemical temephos. Overall, the Ficus extracts proved to be eco-friendly strategies for managing the polyphagous pest Spodoptera litura and are potentially more sustainable and less harmful to non-target earthworms. Nonetheless, in silico predictions suggest that the active compounds in fig extracts are predominantly toxic against honeybees (16 compounds) and violate TICE rules (10 compounds). Therefore, the biological actions of fig extracts' individual novel chemistries need to be examined on target and non-target species to develop better pest management strategies.     

Phosphorylation of multifunctional nucleolar protein nucleophosmin (NPM1) by aurora kinase B is critical for mitotic progression

The functional association of NPM1 with Aurora kinases is well documented. Surprisingly, although NPM1 is a well characterized phosphoprotein, it is unknown whether it is a substrate of Aurora kinases. We have found that Aurora kinases A and B can phosphorylate NPM1 at a single serine residue, Ser125, in vitro and in vivo. Phosphorylated-S125-NPM1 (pS125-NPM1) localizes to the midbody region during late cytokinesis where it colocalizes with Aurora B. The overexpression of mutant (S125A) NPM1 resulted in the deregulation of centrosome duplication and mitotic defects possibly due to cytokinesis failure. These data suggest that Aurora kinase B-mediated phosphorylation of NPM1 plays a critical role during mitosis, which could have wider implications in oncogenesis.