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

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Pocas, Juliana ; Marques, Catarina ; Gomes, Catarina ; Otake, Andreia Hanada ; Pinto, Filipe ; Ferreira, Mariana ; Silva, Tiago ; Faria-Ramos, Isabel ; Matos, Rita ; Ribeiro, Ana Raquel ; Senra, Emanuel ; Cavadas, Bruno ; Batista, Silvia ; Maia, Joana ; Macedo, Joana A. ; Lima, Luis ; Afonso, Luis Pedro ; Ferreira, Jose Alexandre ; Santos, Lucio Lara ; Polonia, Antonio ; Osorio, Hugo ; Belting, Mattias ; Reis, Celso A. ; Costa-Silva, Bruno ; Magalhaes, Ana

• Document type: Journal article
• Source: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; v. 120, n. 20, p. 11-pg., 2023-05-16.

Abstract

Gastric cancer is a dominating cause of cancer-associated mortality with limited therapeutic options. Here, we show that syndecan-4 (SDC4), a transmembrane pro-teoglycan, is highly expressed in intestinal subtype gastric tumors and that this sig -nature 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. (AU)

• FAPESP's process: 19/00740-0 - Exosomes released by pre-metastatic niche-containing liver as mediators of pancreas adenocarcinoma liver metastasis
• Grantee: Andréia Hanada Otake
• Support Opportunities: Scholarships abroad - Research