{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T01:58:27Z","timestamp":1788400707368,"version":"build-2803163510"},"reference-count":58,"publisher":"Wiley","license":[{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"abstract":"<jats:p>\n                    Accumulation of abnormal chondroitin sulfate (CS) chains in breast cancer tissue is correlated with poor prognosis. However, the biological functions of these CS chains in cancer progression remain largely unknown, impeding the development of targeted treatment focused on CS. Previous studies identified chondroitin polymerizing factor (CHPF; also known as chondroitin sulfate synthase 2) is the critical enzyme regulating CS accumulation in breast cancer tissue. We then assessed the association between CHPF\u2010associated proteoglycans (PGs) and signaling pathways in breast cancer datasets. The regulation between CHPF and syndecan 1 (SDC1) was examined at both the protein and RNA levels. Confocal microscopy and image flow cytometry were employed to quantify macropinocytosis. The effects of the 6\u2010\n                    <jats:italic>O<\/jats:italic>\n                    \u2010sulfated CS\u2010binding peptide (C6S\u2010p) on blocking CS functions were tested\n                    <jats:italic>in\u2009vitro<\/jats:italic>\n                    and\n                    <jats:italic>in\u2009vivo<\/jats:italic>\n                    . Results indicated that the expression of\n                    <jats:italic>CHPF<\/jats:italic>\n                    and\n                    <jats:italic>SDC1<\/jats:italic>\n                    was tightly associated within primary breast cancer tissue, and high expression of both genes exacerbated patient prognosis. Transforming growth factor beta (TGF\u2010\u03b2) signaling was implicated in the regulation of CHPF and SDC1 in breast cancer cells. CHPF supported CS\u2013SDC1 stabilization on the cell surface, modulating macropinocytotic activity in breast cancer cells under nutrient\u2010deprived conditions. Furthermore, C6S\u2010p demonstrated the ability to bind CS\u2010SDC1, increase SDC1 degradation, suppress macropinocytosis of breast cancer cells, and inhibit tumor growth\n                    <jats:italic>in\u2009vivo<\/jats:italic>\n                    . Although other PGs may also be involved in CHPF\u2010regulated breast cancer malignancy, this study provides the first evidence that a CS synthase participates in the regulation of macropinocytosis in cancer cells by supporting SDC1 expression on cancer cells.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.13667","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T03:45:02Z","timestamp":1716263102000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Targeting chondroitin sulfate suppresses macropinocytosis of breast cancer cells by modulating syndecan\u20101 expression"],"prefix":"10.1002","author":[{"given":"Hung\u2010Rong","family":"Yen","sequence":"first","affiliation":[{"name":"Department of Chinese Medicine China Medical University Hospital  Taichung Taiwan"},{"name":"Chinese Medicine Research Center, and School of Chinese Medicine, College of Chinese Medicine China 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