Cell fusion enhances energy metabolism of mesenchymal tumor hybrid cells to sustain their proliferation and invasion

Background 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 f...

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Vydáno v:	BMC cancer Ročník 21; číslo 1; s. 1 - 12
Hlavní autoři:	Brito, Ariadna, Merle, Candice, Lagarde, Pauline, Faustin, Benjamin, Devin, Anne, Lartigue, Lydia, Chibon, Frederic
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London BioMed Central 28.07.2021 BioMed Central Ltd Springer Nature B.V BMC
Témata:	AICAR AMP AMPK Bioenergetics Biomedical and Life Sciences Biomedicine Biosynthesis Cancer Cancer cells Cancer Research Cell division Cell fusion Cell growth Cell hybridization Cell proliferation Energy Energy metabolism Environmental conditions Forecasts and trends Gene expression Genomes Glucose Glycolysis Growth Health aspects Health Promotion and Disease Prevention Hybrids Invasion Invasiveness Kinases Life Sciences Medicine/Public Health Mesenchyme Metabolism Metastases Metastasis Oncology Phosphorylation Physiological aspects Protein kinase Respiration Sarcoma Surgical Oncology Tumors France AMPK Energy metabolism AICAR Cell fusion Invasion
ISSN:	1471-2407, 1471-2407
On-line přístup:	Získat plný text
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Popis
Shrnutí:	Background 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. Results 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. Conclusion 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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 PMCID: PMC8317390
ISSN:	1471-2407 1471-2407
DOI:	10.1186/s12885-021-08561-6