Cell fusion enhances energy metabolism of mesenchymal tumor hybrid cells to sustain their proliferation and invasion
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ABSTRACT:
PROVIDER: PRJNA719777 | ENA |
REPOSITORIES: ENA
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Project description:Cell-to-cell fusion is emerging as a key element of the metastatic process in various cancer types. We recently showed that hybrids made from the spontaneous merging of pre-malignant (IMR90 E6E7, i.e. E6E7) and malignant (IMR90 E6E7 RST, i.e. RST) mesenchymal cells recapitulate the main features of human undifferentiated pleomorphic sarcoma (UPS), with a highly rearranged genome and increased spreading capacities. To better characterize the intrinsic properties of these hybrids, we investigated here their metabolic energy profile compared to their parents. Our results unveiled that hybrids harbored a Warburg-like metabolism, like their RST counterparts. However, hybrids displayed a much greater metabolic activity, enhancing glycolysis to proliferate. Interestingly, modifying the metabolic environmental conditions through the use of 5-aminoimidazole-4-carbox-amide-1-β-D-ribofuranoside (AICAR), an activator of the 5’-adenosine monophosphate (AMP)-activated protein kinase (AMPK), specifically reduced the growth of hybrids, and also abrogated the invasive capacity of hybrids displaying enhanced glycolysis. Furthermore, AICAR efficiently blocked the tumoral features related to the aggressiveness of human UPS cell lines. Altogether, our findings strongly suggest that hybrids rely on higher energy flux to proliferate and that a drug altering this metabolic equilibrium could impair their survival and be potentially considered as a novel therapeutic strategy.
2021-08-04 | GSE171471 | GEO
Project description:BackgroundCell-to-cell fusion is emerging as a key element of the metastatic process in various cancer types. We recently showed that hybrids made from the spontaneous merging of pre-malignant (IMR90 E6E7, i.e. E6E7) and malignant (IMR90 E6E7 RST, i.e. RST) mesenchymal cells recapitulate the main features of human undifferentiated pleomorphic sarcoma (UPS), with a highly rearranged genome and increased spreading capacities. To better characterize the intrinsic properties of these hybrids, we investigated here their metabolic energy profile compared to their parents.ResultsOur results unveiled that hybrids harbored a Warburg-like metabolism, like their RST counterparts. However, hybrids displayed a much greater metabolic activity, enhancing glycolysis to proliferate. Interestingly, modifying the metabolic environmental conditions through the use of 5-aminoimidazole-4-carbox-amide-1-β-D-ribofuranoside (AICAR), an activator of the 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK), specifically reduced the growth of hybrids, and also abrogated the invasive capacity of hybrids displaying enhanced glycolysis. Furthermore, AICAR efficiently blocked the tumoral features related to the aggressiveness of human UPS cell lines.ConclusionAltogether, our findings strongly suggest that hybrids rely on higher energy flux to proliferate and that a drug altering this metabolic equilibrium could impair their survival and be potentially considered as a novel therapeutic strategy.
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Project description:Salmonella invasion of non-phagocytic cells is a dynamic process that requires the translocation of effector proteins into host cells by a type III secretion system (T3SS1) encoded on Salmonella pathogenicity island 1 (SPI1). The signals involved in T3SS1 induction in vivo are not known, but SPI1-induced invasive Salmonella can be prepared by growth in synthetic media. Here we compared two different methods of preparing SPI1-induced bacteria by using a combination of transcriptome analysis, a single-cell reporter assay and intracellular gene expression analysis to reveal clear differences between these two bacterial populations that are reflected in their ability to interact with cultured epithelial cells. Invasion efficiency and intracellular replication were greater for bacteria grown with aeration to late-log phase compared to those grown without aeration to stationary phase. No significant differences in SPI1 regulon expression were revealed by transcriptome analysis. By contrast, surface appendage and stress response genes were considerably changed. Single cell analyses of gene expression revealed variation in the frequency of SPI1-induced bacteria and a correlation between SPI1-induction and the presence of flagella. The expression of virulence genes following invasion of cultured epithelial cells was also found to be predetermined by pre-invasion growth conditions. Key words: epithelial, flagella, invasion, motility, Salmonella-containing vacuole, treatment of shaking versus treatment of static growth conditions for St-SL1344
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