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In this work, we report the application of lectin-directed protein aggregation therapy (LPAT) to target hypersialylated and hyperfucosylated colorectal cancer cells. This system relies on the concept of cancer-activated lectin multivalency, where tumor-associated proteases can elicit the self-assembly of multivalent lectin complexes that can selectively impair the metastatic activities of cancer cells. After screening LPAT agents against a panel of 5 colorectal cancer cell lines, the most effective targeting was identified against the hyperfucosylated\/matrix metalloproteinase-9-overexpressing HCT-116 cell line, which showed significant reductions in invasion and migration upon treatment. Experiments then showed that hyperfucosylation targeting could be used as a viable approach to prevent liver and kidney tumor development in a metastatic colorectal mouse model. Overall, this work highlights the viability of using LPAT to discriminate the aberrant glycosylation of highly metastatic colorectal cancer cells as a means to prevent their onset and progression.<\/jats:p>","DOI":"10.34133\/bmr.0394","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T18:56:10Z","timestamp":1782932170000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":0,"title":["Lectin-Directed Protein Aggregation Therapy toward Hyperfucosylated and Hypersialylated Metastatic Colorectal Cancers"],"prefix":"10.34133","volume":"30","author":[{"given":"Xiao","family":"Han","sequence":"first","affiliation":[{"name":"Department of Chemistry, \rThe Hong Kong University of Science and Technology, Hong Kong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Chemistry, \rThe Hong Kong University of Science and Technology, Hong Kong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiling","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, \rThe Hong Kong University of Science and Technology, Hong Kong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenghai","family":"Shen","sequence":"additional","affiliation":[{"name":"Division of Life Science, \rThe Hong Kong University of Science and Technology, Hong Kong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yitong","family":"Shen","sequence":"additional","affiliation":[{"name":"Division of Life Science, \rThe Hong Kong University of Science and Technology, Hong Kong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Sheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, \rThe Hong Kong University of Science and Technology, Hong Kong, China."},{"name":"Division of Life Science, \rThe Hong Kong University of Science and Technology, Hong Kong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8850-5163","authenticated-orcid":true,"given":"Kenward","family":"Vong","sequence":"additional","affiliation":[{"name":"Department of Chemistry, \rThe Hong Kong University of Science and Technology, Hong Kong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-022-00864-3"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2744"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8155"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02120"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.crphar.2021.100079"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2007.00484.x"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1022576712961"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-019-0145-y"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2018.07.026"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21763"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-023-00353-4"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M111.011601"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.3c00833"},{"issue":"5","key":"e_1_3_4_15_2","first-page":"1772","article-title":"Expression of N-acetylglucosaminyltransferase V in colorectal cancer correlates with metastasis and poor prognosis","volume":"6","author":"Murata K","year":"2000","unstructured":"Murata K, Miyoshi E, Kameyama M, Ishikawa O, Kabuto T, Sasaki Y, Hiratsuka M, Ohigashi H, Ishiguro S, Ito S, et al. 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