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Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival

Poças, Juliana ; Marques, Catarina ; Gomes, Catarina ; Otake, Andreia Hanada ; Pinto, Filipe ; Ferreira, Mariana ; Silva, Tiago ; Faria-Ramos, Isabel ; Matos, Rita and Ribeiro, Ana Raquel , et al. (2023) In Proceedings of the National Academy of Sciences of the United States of America 120(20).
Abstract

Gastric cancer is a dominating cause of cancer-associated mortality with limited therapeutic options. Here, we show that syndecan-4 (SDC4), a transmembrane proteoglycan, is highly expressed in intestinal subtype gastric tumors and that this signature associates with patient poor survival. Further, we mechanistically demonstrate that SDC4 is a master regulator of gastric cancer cell motility and invasion. We also find that SDC4 decorated with heparan sulfate is efficiently sorted in extracellular vesicles (EVs). Interestingly, SDC4 in EVs regulates gastric cancer cell-derived EV organ distribution, uptake, and functional effects in recipient cells. Specifically, we show that SDC4 knockout disrupts the tropism of EVs for the common... (More)

Gastric cancer is a dominating cause of cancer-associated mortality with limited therapeutic options. Here, we show that syndecan-4 (SDC4), a transmembrane proteoglycan, is highly expressed in intestinal subtype gastric tumors and that this signature associates with patient poor survival. Further, we mechanistically demonstrate that SDC4 is a master regulator of gastric cancer cell motility and invasion. We also find that SDC4 decorated with heparan sulfate is efficiently sorted in extracellular vesicles (EVs). Interestingly, SDC4 in EVs regulates gastric cancer cell-derived EV organ distribution, uptake, and functional effects in recipient cells. Specifically, we show that SDC4 knockout disrupts the tropism of EVs for the common gastric cancer metastatic sites. Our findings set the basis for the molecular implications of SDC4 expression in gastric cancer cells and provide broader perspectives on the development of therapeutic strategies targeting the glycan-EV axis to limit tumor progression.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Proceedings of the National Academy of Sciences of the United States of America
volume
120
issue
20
article number
e2214853120
publisher
National Academy of Sciences
external identifiers
  • pmid:37155874
  • scopus:85158135443
ISSN
0027-8424
DOI
10.1073/pnas.2214853120
language
English
LU publication?
yes
id
e1d3d19e-f007-4245-a2bf-29e92cd240c3
date added to LUP
2023-08-10 12:54:02
date last changed
2024-07-13 07:50:48
@article{e1d3d19e-f007-4245-a2bf-29e92cd240c3,
  abstract     = {{<p>Gastric cancer is a dominating cause of cancer-associated mortality with limited therapeutic options. Here, we show that syndecan-4 (SDC4), a transmembrane proteoglycan, is highly expressed in intestinal subtype gastric tumors and that this signature associates with patient poor survival. Further, we mechanistically demonstrate that SDC4 is a master regulator of gastric cancer cell motility and invasion. We also find that SDC4 decorated with heparan sulfate is efficiently sorted in extracellular vesicles (EVs). Interestingly, SDC4 in EVs regulates gastric cancer cell-derived EV organ distribution, uptake, and functional effects in recipient cells. Specifically, we show that SDC4 knockout disrupts the tropism of EVs for the common gastric cancer metastatic sites. Our findings set the basis for the molecular implications of SDC4 expression in gastric cancer cells and provide broader perspectives on the development of therapeutic strategies targeting the glycan-EV axis to limit tumor progression.</p>}},
  author       = {{Poças, Juliana and Marques, Catarina and Gomes, Catarina and Otake, Andreia Hanada and Pinto, Filipe and Ferreira, Mariana and Silva, Tiago and Faria-Ramos, Isabel and Matos, Rita and Ribeiro, Ana Raquel and Senra, Emanuel and Cavadas, Bruno and Batista, Sílvia and Maia, Joana and Macedo, Joana A. and Lima, Luís and Afonso, Luís Pedro and Ferreira, José Alexandre and Santos, Lúcio Lara and Polónia, António and Osório, Hugo and Belting, Mattias and Reis, Celso A. and Costa-Silva, Bruno and Magalhães, Ana}},
  issn         = {{0027-8424}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{20}},
  publisher    = {{National Academy of Sciences}},
  series       = {{Proceedings of the National Academy of Sciences of the United States of America}},
  title        = {{Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival}},
  url          = {{http://dx.doi.org/10.1073/pnas.2214853120}},
  doi          = {{10.1073/pnas.2214853120}},
  volume       = {{120}},
  year         = {{2023}},
}