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Tissue inhibitor of metalloproteinases 2 (TIMP\u20102) has been shown to be associated with colorectal cancer (CRC), but its correlation with 5\u2010Fu resistance in colorectal cancer has not been thoroughly studied. We screen the expression of different cytokines through Cytokine array. CCK\u20108 assay was conducted to evaluate the IC<jats:sub>50<\/jats:sub> of 5\u2010Fu and cell proliferation. ELISA and RT\u2010qPCR were performed to detect TIMP\u20102 expression levels in cells and patient serum. Western blotting was utilised to analyse the differences in the expression of proteins related to signalling pathways in cells. Through cytokine array screening, we found that the expression of TIMP\u20102 was significantly increased in CRC drug\u2010resistant cell lines. In addition, the expression of TIMP\u20102 in the serum of patients with CRC resistance to 5\u2010Fu was significantly increased. Subsequent mechanistic experiments showed that TIMP\u20102 regulated the resistance of CRC cells to 5\u2010Futhrough the JAK\u2013STAT signalling pathway. Moreover, anti\u2010TIMP\u20102 antibody or small molecule drug LY2784544 targeting the JAK\u2013STAT signalling pathway can effectively reverse the resistance of CRC cells to 5\u2010Fu. It is exactly TIMP\u20102 that mediates the resistance of CRC to 5\u2010Fu through the JAK\u2013STAT signalling pathway. Targeting drugs for TIMP\u20102 or the JAK\u2013STAT signalling pathway are expected to be opportunities to reverse 5\u2010Fu resistance in CRC.<\/jats:p>","DOI":"10.1111\/jcmm.70470","type":"journal-article","created":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T14:23:51Z","timestamp":1742739831000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["<scp>TIMP<\/scp>\u20102 Modulates 5\u2010Fu Resistance in Colorectal Cancer Through Regulating <scp>JAK<\/scp>\u2013<scp>STAT<\/scp> Signalling Pathway"],"prefix":"10.1111","volume":"29","author":[{"given":"Chuchu","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery Shaoxing People's Hospital  Shaoxing Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renjun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Emergency Shaoxing People's Hospital  Shaoxing Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingfeng","family":"Dai","sequence":"additional","affiliation":[{"name":"Zhijiang College, Zhejiang University of Technolog  Shaoxing Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoqing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery Shaoxing People's Hospital  Shaoxing Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gengyuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery Shaoxing People's Hospital  Shaoxing Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelong","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery Shaoxing People's Hospital  Shaoxing Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gynaecology Shaoxing People's Hospital  Shaoxing Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangen","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery Shaoxing People's Hospital  Shaoxing Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5836-4478","authenticated-orcid":false,"given":"Guolin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery Shaoxing People's Hospital  Shaoxing Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.0106"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21654"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(19)32319\u20100"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1074"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111285"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.14532"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2016.91"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033\u2010022\u201007227\u20101"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2019.107447"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/5874127"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032\u2010015\u20100703\u2010y"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010021\u201001428\u20101"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326\u20106066.cir\u201014\u20100160"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2016.03.005"},{"key":"e_1_2_12_17_1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1023\/A:1025819214508","article-title":"Matrix Metalloproteinases in Colorectal Cancer: Is It Worth Talking About?","volume":"23","author":"Wagenaar\u2010Miller R. 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