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Glycosphingolipids are mediators of cancer plasticity through independent signaling pathways

The molecular repertoire promoting cancer cell plasticity is not fully elucidated. Here, we propose that glycosphingolipids (GSLs), specifically the globo and ganglio series, correlate and promote the transition between epithelial and mesenchymal cells. The epithelial character of ovarian cancer rem...

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Main Authors: Cumin, Cécile (Author) , Huang, Yen-Lin (Author) , Rossdam, Charlotte (Author) , Ruoff, Felix (Author) , Céspedes, Susana Posada (Author) , Liang, Ching-Yeu (Author) , Lombardo, Flavio C. (Author) , Coelho, Ricardo (Author) , Rimmer, Natalie (Author) , Konantz, Martina (Author) , López, Mónica Núñez (Author) , Alam, Md Shahidul (Author) , Schmidt, Alexander (Author) , Calabrese, Diego (Author) , Fedier, Andre (Author) , Vlajnic, Tatjana (Author) , von Itzstein, Mark (Author) , Templin, Markus (Author) , Buettner, Falk F. R. (Author) , Everest-Dass, Arun (Author) , Heinzelmann-Schwarz, Viola (Author) , Jacob, Francis (Author)
Format: Article (Journal)
Language:English
Published: August 16, 2022
In: Cell reports
Year: 2022, Volume: 40, Issue: 7, Pages: 1-16
ISSN:2211-1247
DOI:10.1016/j.celrep.2022.111181
Online Access:Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.celrep.2022.111181
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S2211124722009949
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Author Notes:Cécile Cumin, Yen-Lin Huang, Charlotte Rossdam, Felix Ruoff, Susana Posada Céspedes, Ching-Yeu Liang, Flavio C. Lombardo, Ricardo Coelho, Natalie Rimmer, Martina Konantz, Mónica Núñez López, Shahidul Alam, Alexander Schmidt, Diego Calabrese, Andre Fedier, Tatjana Vlajnic, Mark von Itzstein, Markus Templin, Falk F. R. Buettner, Arun Everest-Dass, Viola Heinzelmann-Schwarz, and Francis Jacob

MARC

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520 |a The molecular repertoire promoting cancer cell plasticity is not fully elucidated. Here, we propose that glycosphingolipids (GSLs), specifically the globo and ganglio series, correlate and promote the transition between epithelial and mesenchymal cells. The epithelial character of ovarian cancer remains stable throughout disease progression, and spatial glycosphingolipidomics reveals elevated globosides in the tumor compartment compared with the ganglioside-rich stroma. CRISPR-Cas9 knockin mediated truncation of endogenous E-cadherin induces epithelial-to-mesenchymal transition (EMT) and decreases globosides. The transcriptomics analysis identifies the ganglioside-synthesizing enzyme ST8SIA1 to be consistently elevated in mesenchymal-like samples, predicting poor outcome. Subsequent deletion of ST8SIA1 induces epithelial cell features through mTORS2448 phosphorylation, whereas loss of globosides in ΔA4GALT cells, resulting in EMT, is accompanied by increased ERKY202/T204 and AKTS124. The GSL composition dynamics corroborate cancer cell plasticity, and further evidence suggests that mesenchymal cells are maintained through ganglioside-dependent, calcium-mediated mechanisms. 
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