{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Harmych SJ"],"funding":["U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)","U.S. Department of Health & Human Services | National Institutes of Health (NIH)","U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)"],"pagination":["1261"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12373842"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["8(1)"],"pubmed_abstract":["Loss of polarity is a hallmark of cancer, and the related epithelial-to-mesenchymal transition (EMT) phenotype impacts prognosis and therapy outcomes, particularly in colorectal cancer (CRC). However, the mechanisms and drugs that impact EMT-related morphological changes are understudied, due to the complete failure of typical live/dead 2D high-throughput screens to capture morphology or the lack of robustness of 3D screens. We designed a high-throughput screen using 3D type I collagen cultures of CRC cells to assess morphological changes in colonies and identified several FDA-approved drugs that re-epithelialize CRC colonies. One of these drugs, azithromycin, increased colony circularity, enhanced E-cadherin membrane localization and ZO-1 localization to tight junctions, caused transcriptomic changes consistent with downregulation of EMT, and elevated sensitivity to the chemotherapeutic, irinotecan. A retrospective analysis of patient data demonstrated that the use of azithromycin in patients undergoing treatment for CRC with irinotecan had improved the 5 year survival compared to the chemotherapy alone. These results highlight the importance of morphological screens to identify novel drug candidates and synergistic mechanisms."],"journal":["Communications biology"],"pubmed_title":["3D collagen high-throughput screen identifies drugs that induce epithelial polarity and enhance chemotherapy response in colorectal cancer."],"pmcid":["PMC12373842"],"funding_grant_id":["R01DK103831","S10OD028719","R50CA211206","S10OD028715","U01CA294527","T32GM07628","P50 236733"],"pubmed_authors":["Bauer JA","Sievers CK","Wahoski CC","Kang SW","Jones VT","Coffey RJ","Liu Q","Ramirez MA","Hasaka TP","Kovtun O","Singh B","Harmych SJ","Zhao Z","Lau KS"],"additional_accession":[]},"is_claimable":false,"name":"3D collagen high-throughput screen identifies drugs that induce epithelial polarity and enhance chemotherapy response in colorectal cancer.","description":"Loss of polarity is a hallmark of cancer, and the related epithelial-to-mesenchymal transition (EMT) phenotype impacts prognosis and therapy outcomes, particularly in colorectal cancer (CRC). However, the mechanisms and drugs that impact EMT-related morphological changes are understudied, due to the complete failure of typical live/dead 2D high-throughput screens to capture morphology or the lack of robustness of 3D screens. We designed a high-throughput screen using 3D type I collagen cultures of CRC cells to assess morphological changes in colonies and identified several FDA-approved drugs that re-epithelialize CRC colonies. One of these drugs, azithromycin, increased colony circularity, enhanced E-cadherin membrane localization and ZO-1 localization to tight junctions, caused transcriptomic changes consistent with downregulation of EMT, and elevated sensitivity to the chemotherapeutic, irinotecan. A retrospective analysis of patient data demonstrated that the use of azithromycin in patients undergoing treatment for CRC with irinotecan had improved the 5 year survival compared to the chemotherapy alone. These results highlight the importance of morphological screens to identify novel drug candidates and synergistic mechanisms.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-05-08T06:51:17.544Z","creation":"2026-04-07T23:31:03.845Z"},"accession":"S-EPMC12373842","cross_references":{"pubmed":["40847193"],"doi":["10.1038/s42003-025-08699-0"]}}