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Sialyl-Tn antigen facilitates extracellular vesicle-mediated transfer of FAK and enhances motility of recipient cells

Title: Sialyl-Tn antigen facilitates extracellular vesicle-mediated transfer of FAK and enhances motility of recipient cells
Authors: Nagao, Keisuke; Maeda, Kento; Hosomi, Kasumi; Morioka, Kaito; Inuzuka, Tatsutoshi; Ohtsubo, Kazuaki
Source: The Journal of Biochemistry ; volume 171, issue 5, page 543-554 ; ISSN 0021-924X 1756-2651
Publisher Information: Oxford University Press (OUP)
Publication Year: 2022
Description: Protein glycosylation plays a pivotal role in tumour development by modulating molecular interactions and cellular signals. Sialyl-Tn (sTn) antigen is a tumour-associating carbohydrate epitope whose expression correlates with metastasis and poor prognosis of various cancers; however, its pathophysiological function is poorly understood. Extracellular vesicles (EVs) derived from cancer cells act as a signal mediator amongst tumour microenvironments by transferring cargo molecules. sTn antigen has been found in the glycans of EVs, thereby the functional relevance of sTn antigen to the regulation of tumour microenvironments could be expected. In the present study, we showed that sTn antigen induced TP53 and tumour suppressor–activated pathway 6 (TSAP6) and consequently enhanced EV production. Besides, the genetic attenuation of TSAP6 resulted in the reduction of the EV production in the sTn antigen expressing cells. The enhanced EV production in the sTn antigen–expressing cells consequently augmented the delivery of EVs to recipient cells. The produced EVs selectively and abundantly encased focal adhesion kinase and transferred it to EV-recipient cells, and thus, their cellular motility was enhanced. These findings would contribute to facilitate the elucidation of the pathophysiological significance of the sTn antigen in the tumour microenvironments and tumour development.
Document Type: article in journal/newspaper
Language: English
DOI: 10.1093/jb/mvac008
DOI: 10.1093/jb/mvac008/42687591/mvac008.pdf
Availability: https://doi.org/10.1093/jb/mvac008; https://academic.oup.com/jb/advance-article-pdf/doi/10.1093/jb/mvac008/42687591/mvac008.pdf; https://academic.oup.com/jb/article-pdf/171/5/543/43750527/mvac008.pdf
Rights: https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model
Accession Number: edsbas.1BFA7A0C
Database: BASE