{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:01:25Z","timestamp":1790892085665,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Tumor\u2010associated macrophages (TAMs), particularly the M2 subtype, foster immune suppression and metastasis in colorectal cancer (CRC). Although WNT2 is upregulated in several cancers and RUNX1 is an oncogenic transcription factor in solid tumors, whether a RUNX1\u2010WNT2 axis orchestrates M2 polarization and CRC progression has been unclear. We profiled RUNX1 and WNT2 expressions and correlations with M2 markers in TCGA_COAD\/READ using GEPIA and validated findings in 36 paired CRC and adjacent tissues by qRT\u2010PCR, Western blotting, and immunohistochemistry. Functional effects of WNT2 were tested in CRC cell lines (SW480, SW620) using CCK\u20108, colony formation, and Transwell assays after shRNA knockdown. A Transwell co\u2010culture with PMA\u2010differentiated THP\u20101 macrophages assessed polarization by flow cytometry (CD86, CD206) and Western blotting (CD68, MAC2, CD20), alongside ELISAs for CCL2, CSF1, and IL\u201010. RUNX1 regulation of WNT2 was examined by JASPAR\/UCSC prediction, ChIP\u2010qPCR, and dual\u2010luciferase reporter assays. In vivo, we evaluated tumor growth (subcutaneous xenografts) and lung metastasis (tail\u2010vein injection) following WNT2 knockdown and performed rescue studies using an IL\u201010 neutralizing antibody or the CSF1R inhibitor BLZ945. WNT2 was significantly overexpressed in CRC versus normal tissues and positively associated with M2\u2010TAM signatures. WNT2 knockdown curtailed CRC cell viability, clonogenicity, migration, and invasion, reduced secretion of CCL2\/CSF1\/IL\u201010 and shifted THP\u20101 macrophages from an M2\u2010like (CD206\u207a) toward an M1\u2010like (CD86\u207a) phenotype. RUNX1 expression correlated with WNT2; RUNX1 loss decreased WNT2, while overexpression increased it. ChIP and reporter assays demonstrated direct RUNX1 binding and transcriptional activation of the WNT2 promoter. In vivo, WNT2 silencing reduced tumor volume and weight, increased CD86\u207a and decreased CD206\u207a macrophages in tumors, and diminished lung metastatic burden. Furthermore, blocking M2 polarization (anti\u2010IL\u201010) or depleting macrophages (BLZ945) mitigated WNT2\u2010driven tumor growth and M2 infiltration. RUNX1 directly activates WNT2 to promote cytokine production and M2 macrophage polarization, thereby accelerating CRC growth and metastasis. These findings suggest that targeting the RUNX1\u2010WNT2 axis and its downstream macrophage programs may offer a therapeutic strategy and potential biomarker framework for CRC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mc.70116","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T19:09:54Z","timestamp":1776280194000},"page":"825-839","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["RUNX1 Directly Activates WNT2 to Orchestrate Tumor\u2010Associated Macrophage Reprogramming in Colorectal Cancer"],"prefix":"10.1002","volume":"65","author":[{"given":"Wei","family":"Sun","sequence":"first","affiliation":[{"name":"Department of General Medicine, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences Cancer Hospital Affiliated to Shanxi Medical University Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences Cancer Hospital Affiliated to Shanxi Medical University Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqing","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences Cancer Hospital Affiliated to Shanxi Medical University Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingzhi","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences Cancer Hospital Affiliated to Shanxi Medical University Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences Cancer Hospital Affiliated to Shanxi Medical University Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolu","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Radiation Therapy, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences Cancer Hospital Affiliated to Shanxi Medical University Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0805-8958","authenticated-orcid":false,"given":"Yong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ultrasound Imaging, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences Cancer Hospital Affiliated to Shanxi Medical University Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000002108"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2024.116393"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2015.4108"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina56010015"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2020.06.081"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-0134-x"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-021-00366-w"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12345"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46735-5"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-024-00775-4"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.583084"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.888713"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22136995"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1252510"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-004219"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-025-02142-w"},{"issue":"3","key":"e_1_2_12_19_1","first-page":"2857","article-title":"Wnt2 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