{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:16:12Z","timestamp":1785417372600,"version":"3.56.0"},"reference-count":33,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82171565"],"award-info":[{"award-number":["82171565"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82371586"],"award-info":[{"award-number":["82371586"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82171565"],"award-info":[{"award-number":["82171565"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82371586"],"award-info":[{"award-number":["82371586"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Shanghai Municipal Health Commission Project","award":["202140148"],"award-info":[{"award-number":["202140148"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Colorectal cancer (CRC) progression is driven by dysregulated signaling networks that promote proliferation and metastasis. While SLC25A5 is a well-characterized mitochondrial ADP\/ATP transporter, its potential non-canonical roles in cancer remain unclear. This study investigated whether SLC25A5 exerts tumor-suppressive functions in CRC. Using transcriptomic datasets and clinical cohorts, we found that SLC25A5 is significantly downregulated in CRC tissues, and low expression is associated with poor patient survival. Restoration of SLC25A5 suppressed CRC cell proliferation, epithelial\u2013mesenchymal transition (EMT), and metastasis in vitro and in vivo. Mechanistically, co-immunoprecipitation and protein stability assays suggested an association between SLC25A5 and EIF3A and indicated that SLC25A5 may promote EIF3A destabilization through the ubiquitin\u2013proteasome pathway without altering its mRNA levels. Subcellular fractionation further suggested the presence of a cytoplasmic pool of SLC25A5, providing a potential basis for this interaction. Rescue experiments showed that EIF3A overexpression partially reversed the tumor-suppressive effects of SLC25A5. In addition, SLC25A5 expression was associated with reduced PI3K\/AKT signaling activity, and pharmacological activation of AKT partially restored invasive phenotypes. Collectively, these findings suggest an SLC25A5\u2013EIF3A\u2013PI3K\/AKT regulatory axis and reveal a potential non-canonical role for this mitochondrial carrier in tumor progression. This study provides insight into how mitochondrial proteins may influence cytoplasmic signaling pathways in cancer.<\/jats:p>","DOI":"10.3390\/ijms27104334","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T16:26:37Z","timestamp":1778689597000},"page":"4334","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SLC25A5 Suppresses Colorectal Cancer Growth and Metastasis Through Regulation of the EIF3A\/PI3K\/AKT Axis"],"prefix":"10.3390","volume":"27","author":[{"given":"Ke","family":"Ying","sequence":"first","affiliation":[{"name":"School of Medicine, Tongji University, Shanghai 200070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Medicine, Tongji University, Shanghai 200070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medicine, Tongji University, Shanghai 200070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Medicine, Tongji University, Shanghai 200070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medicine, Tongji University, Shanghai 200070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4447-7817","authenticated-orcid":false,"given":"Zhongchen","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medicine, Tongji University, Shanghai 200070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"ref_1","first-page":"233","article-title":"Colorectal cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. 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