{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:43:26Z","timestamp":1786977806153,"version":"build-2736575974"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2023J011770"],"award-info":[{"award-number":["2023J011770"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2023J011785"],"award-info":[{"award-number":["2023J011785"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mantle cell lymphoma (MCL) is a rare and aggressive form of non\u2010Hodgkin lymphoma. Challenges in its treatment include relapse, drug resistance, and a short survival period. The Hedgehog\/GLI1 (Hh\/GLI1) and Wnt\/\u03b2\u2010catenin pathways are crucial in cancer cell proliferation, survival, and drug resistance, making them significant targets for anticancer research. This study aimed to assess the effectiveness of combining inhibitors for both pathways against MCL and investigate the underlying molecular mechanisms. The co\u2010expression of key proteins from the Hh\/GLI1 and Wnt\/\u03b2\u2010catenin pathways was observed in MCL. Targeting the Hh\/GLI1 pathway with the GLI1 inhibitor GANT61 and the Wnt\/\u03b2\u2010catenin pathway with the CBP\/\u03b2\u2010catenin transcription inhibitor ICG\u2010001, dual\u2010target therapy was demonstrated to synergistically suppressed the activity of MCL cells. This approach promoted MCL cell apoptosis, induced G0\/G1 phase blockade, decreased the percentage of S\u2010phase cells, and enhanced the sensitivity of MCL cells to the drugs adriamycin and ibrutinib. Both GANT61 and ICG\u2010001 downregulated GLI1 and \u03b2\u2010catenin while upregulating GSK\u20103\u03b2 expression. The interaction between Hh\/GLI1 and Wnt\/\u03b2\u2010catenin pathways was mediated by GANT61\u2010dependent Hh\/GLI1 inhibition. Moreover, GLI1 knockdown combined with ICG\u2010001 synergistically induced apoptosis and increased drug sensitivity of MCL cells to doxorubicin and ibrutinib. GANT61 attenuated the overexpression of \u03b2\u2010catenin and decreased the inhibition of GSK\u20103\u03b2 in MCL cells. Overall, the combined targeting of both the Hh\/GLI1 and Wnt\/\u03b2\u2010catenin pathways was more effective in suppressing proliferation, inducing G0\/G1 cycle retardation, promoting apoptosis, and increasing drug sensitivity of MCL cells than mono treatments. These findings emphasize the potential of combinatorial therapy for treating MCL patients.<\/jats:p>","DOI":"10.1002\/hon.3305","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T03:39:27Z","timestamp":1724902767000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Combined targeting of Hedgehog\/GLI1 and Wnt\/\u03b2\u2010catenin pathways in mantle cell lymphoma"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6453-3609","authenticated-orcid":false,"given":"Yan","family":"Han","sequence":"first","affiliation":[{"name":"Department of Hematology Quanzhou First Hospital Affiliated to Fujian Medical University  Quanzhou China"},{"name":"Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuntuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology Quanzhou 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