TY - JOUR
T1 - Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival
AU - Poças, Juliana
AU - Marques, Catarina
AU - Gomes, Catarina
AU - Otake, Andreia Hanada
AU - Pinto, Filipe
AU - Ferreira, Mariana
AU - Silva, Tiago
AU - Faria-Ramos, Isabel
AU - Matos, Rita
AU - Ribeiro, Ana Raquel
AU - Senra, Emanuel
AU - Cavadas, Bruno
AU - Batista, Sílvia
AU - Maia, Joana
AU - Macedo, Joana A.
AU - Lima, Luís
AU - Afonso, Luís Pedro
AU - Ferreira, José Alexandre
AU - Santos, Lúcio Lara
AU - Polónia, António
AU - Osório, Hugo
AU - Belting, Mattias
AU - Reis, Celso A.
AU - Costa-Silva, Bruno
AU - Magalhães, Ana
PY - 2023/5/16
Y1 - 2023/5/16
N2 - 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.
AB - 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.
U2 - 10.1073/pnas.2214853120
DO - 10.1073/pnas.2214853120
M3 - Article
C2 - 37155874
AN - SCOPUS:85158135443
SN - 0027-8424
VL - 120
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 20
M1 - e2214853120
ER -
