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However, current studies mostly focus on exosomal RNA and proteins and lack an in\u2010depth exploration of exosomal DNA. It is discovered that\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    <jats:sup>H1047R<\/jats:sup>\n                    mutant DNA in colorectal cancer (CRC) cell\u2010derived exosomes can be delivered into recipient fibroblasts, where they are transcribed and translated, ultimately leading to the activation of fibroblasts into cancer\u2010associated fibroblasts (CAFs) through interaction with the endogenous P85 regulatory subunit of the phosphatidylinositol 3\u2010kinase (PI3K) pathway. CAFs have facilitated tumor cell migration in vitro and promote lung metastasis in vivo by secreting elevated levels of IL6. Additionally, the\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    <jats:sup>H1047R<\/jats:sup>\n                    mutation is detected in CAFs at both the primary and metastatic sites, suggesting that it may play a role in promoting metastasis by influencing the TME. Moreover, patients with CRC harboring the\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    <jats:sup>H1047R<\/jats:sup>\n                    mutation and exhibiting elevated levels of IL6 are significantly more likely to metastasize. These findings suggest that the simultaneous detection of serum\u2010derived exosomal\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    <jats:sup>H1047R<\/jats:sup>\n                    mutation and serum IL6 secretion may serve as a promising diagnostic and prognostic tool for CRC and simultaneous targeting of\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    <jats:sup>H1047R<\/jats:sup>\n                    mutation and IL6 may serve as a novel approach for the treatment of CRC.\n                  <\/jats:p>","DOI":"10.1002\/advs.202501792","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T08:41:45Z","timestamp":1748335305000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Colorectal Cancer Cells\u2013Derived Exosomal\n                    <i>PIK3CA<\/i>\n                    Mutation DNA Promotes Tumor Metastasis by Activating Fibroblast and Affecting Tumor Metastatic Microenvironment"],"prefix":"10.1002","volume":"12","author":[{"given":"Rui","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cell Biology Key Laboratory of Cell Biology Ministry of Public Health Key Laboratory of Medical Cell Biology Ministry of Education China Medical University  Shenyang 110122 China"},{"name":"Department of Stem Cells and Regenerative Medicine Key Laboratory of Cell Biology Ministry of Public Health Key Laboratory of Medical Cell Biology Ministry of Education China Medical University  Shenyang 110122 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanming","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Key Laboratory of Cell Biology Ministry of Public Health Key Laboratory of Medical Cell Biology Ministry of Education China Medical University  Shenyang 110122 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoshuai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion Shengjing Hospital of China Medical University  Shenyang 110000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5188-5206","authenticated-orcid":false,"given":"Jin","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Key Laboratory of Cell Biology Ministry of Public Health Key Laboratory of Medical Cell Biology Ministry of Education China Medical University  Shenyang 110122 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