{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T11:01:08Z","timestamp":1784286068060,"version":"3.55.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T00:00:00Z","timestamp":1639699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer owing to a lack of effective targeted therapy and acquired chemoresistance. Here, we explored the function and mechanism of shank-interacting protein-like 1 (SIPL1) in TNBC progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>SIPL1 expression was examined in human TNBC tissues and cell lines by quantitative reverse transcription PCR, western blot, and immunohistochemistry. <jats:italic>SIPL1<\/jats:italic> overexpression and silenced cell lines were established in BT-549 and MDA-MB-231 cells. The biological functions of SIPL1 in TNBC were studied <jats:italic>in vitro<\/jats:italic> using the CCK-8 assay, CellTiter-Glo Luminescent Cell Viability assay, caspase-3\/8\/9 assay, wound healing assay, and transwell assay and <jats:italic>in vivo<\/jats:italic> using a nude mouse model. The potential mechanisms underlying the effects of SIPL1 on TNBC progression were explored using bioinformatics analysis, luciferase reporter assays, and chromatin immunoprecipitation followed by qPCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>SIPL1<\/jats:italic> expression was higher in human TNBC tissues and cell lines than in adjacent normal tissues and a breast epithelial cell line (MCF10A). High expression of <jats:italic>SIPL1<\/jats:italic> was positively correlated with poor overall and disease-free survival in patients with TNBC. <jats:italic>SIPL1<\/jats:italic> overexpression elevated and <jats:italic>SIPL1<\/jats:italic> silencing repressed the malignant phenotypes of TNBC cells <jats:italic>in vitro<\/jats:italic>. <jats:italic>SIPL1<\/jats:italic> overexpression promoted xenograft tumor growth <jats:italic>in vivo<\/jats:italic>. Myc-associated zinc-finger protein (MAZ) transcriptionally activated <jats:italic>SIPL1<\/jats:italic>. Finally, we found that SIPL1 promoted TNBC malignant phenotypes <jats:italic>via<\/jats:italic> activation of the AKT\/NF-\u03baB signaling pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results indicate that the MAZ\/SIPL1\/AKT\/NF-\u03baB axis plays a crucial role in promoting the malignant phenotypes of TNBC cells.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2021.766790","type":"journal-article","created":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T08:03:06Z","timestamp":1639728186000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["SIPL1, Regulated by MAZ, Promotes Tumor Progression and Predicts Poor Survival in Human Triple-Negative Breast 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