Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival
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, w...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2023-05, Vol.120 (20), p.1 |
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| creator | Poças, 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, Sílvia Maia, Joana Macedo, Joana A Lima, Luís Afonso, Luís Pedro Ferreira, José Alexandre Santos, Lúcio Lara Polónia, António Osório, Hugo Belting, Mattias Reis, Celso A Costa-Silva, Bruno Magalhães, Ana |
| description | 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. |
| doi_str_mv | 10.1073/pnas.221485312 |
| format | Article |
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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. 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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.</description><subject>Cancer</subject><subject>Cell interactions</subject><subject>Gastric cancer</subject><subject>Glycan</subject><subject>Heparan sulfate</subject><subject>Metastases</subject><subject>Proteoglycans</subject><subject>Survival</subject><subject>Syndecan</subject><subject>Tropism</subject><subject>Tumors</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNqNjcFOwzAQRC0EEgF67Xklzilrx02TMwJxh3u1cl3qKvGm3jhS_x4j8QGcZjRvNKPUWuNG4655mSLJxhhtu22jzY2qNPa6bm2Pt6pCNLu6s8beqweRMyL22w4rdfq8xoN3FGsLQYBgJC9zYuAjfFNxwUGhzidwfhggxIUkcASKB3A8jjkGR_NvMp9ohlzWkjhOXmBiTiA5LWGh4UndHWkQv_rTR_X8_vb1-lFPiS-5fO7PnFMsaG863epGt8Y2_2v9AJpoTsE</recordid><startdate>20230516</startdate><enddate>20230516</enddate><creator>Poças, Juliana</creator><creator>Marques, Catarina</creator><creator>Gomes, Catarina</creator><creator>Otake, Andreia Hanada</creator><creator>Pinto, Filipe</creator><creator>Ferreira, Mariana</creator><creator>Silva, Tiago</creator><creator>Faria-Ramos, Isabel</creator><creator>Matos, Rita</creator><creator>Ribeiro, Ana Raquel</creator><creator>Senra, Emanuel</creator><creator>Cavadas, Bruno</creator><creator>Batista, Sílvia</creator><creator>Maia, Joana</creator><creator>Macedo, Joana A</creator><creator>Lima, Luís</creator><creator>Afonso, Luís Pedro</creator><creator>Ferreira, José Alexandre</creator><creator>Santos, Lúcio Lara</creator><creator>Polónia, António</creator><creator>Osório, Hugo</creator><creator>Belting, Mattias</creator><creator>Reis, Celso A</creator><creator>Costa-Silva, Bruno</creator><creator>Magalhães, Ana</creator><general>National Academy of Sciences</general><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20230516</creationdate><title>Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival</title><author>Poças, Juliana ; 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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.</abstract><cop>Washington</cop><pub>National Academy of Sciences</pub><doi>10.1073/pnas.221485312</doi></addata></record> |
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| source | PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Cancer Cell interactions Gastric cancer Glycan Heparan sulfate Metastases Proteoglycans Survival Syndecan Tropism Tumors |
| title | Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival |
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