Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival
(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.
(Less)
- author
- organization
- publishing date
- 2023-05-16
- 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}}, }