ArticleThe Journal of international medical research2025
PERP suppresses breast cancer metastasis via the ATF3-HSPA6 signaling pathway.
Article in The Journal of international medical research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
ObjectiveThe role of the tumor suppressor p53 apoptosis effector related to PMP-22 (PERP) in breast cancer metastasis remains unclear. This study investigated PERP's role in metastatic progression, its clinical significance, and the mechanisms underlying its effects.MethodsPERP expression was assessed in breast cancer cell lines, public datasets, and 142 patient samples using real-time quantitative polymerase chain reaction (RT-qPCR), western blotting, and immunohistochemistry. In vitro migration and invasion assays as well as in vivo metastasis model were performed after PERP overexpression or knockdown in MDA-MB-231 and MCF-7 cells. The roles of activating transcription factor 3 (ATF3) and heat shock protein family A member 6 (HSPA6) were evaluated through small-interfering RNA-mediated modulation, RNA sequencing, western blotting, RT-qPCR, and chromatin immunoprecipitation.ResultsPERP expression was markedly reduced in breast cancer cells and tumor tissues compared with that in normal controls, and low PERP levels were associated with poor prognosis. PERP overexpression suppressed metastasis. Mechanistically, PERP upregulated ATF3 expression, and ATF3 bound to the HSPA6 promoter to activate its transcription. Knockdown of
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