Esophageal cancer (EC) is associated with high mortality rates and widespread resistance to chemotherapeutic agents, like paclitaxel (PTX), posing a significant global public health challenge. ANP32E is a member of the acidic nuclear phosphoprotein 32 family, its specific biological functions and mechanisms in EC remain unclear. Through bioinformatics analysis and clinical tissue sample studies, we observed a marked upregulation of ANP32E expression in EC tissues. Utilizing ANP32E knock-out EC cell models and xenograft experiments in nude mice, we demonstrated that the absence of ANP32E significantly inhibits tumor progression and migration, whereas its overexpression exacerbates tumor growth. Transcriptomic sequencing (RNA-seq) further revealed activation of the ferroptosis pathway in ANP32E deficient cells, which was confirmed through experiments showing enhanced ferroptosis that could be reversed by the ferroptosis inhibitor ferrostatin-1. At the molecular level, ANP32E regulates EC progression and ferroptosis via the p53/SLC7A11 axis. ANP32E depletion resulted in increased p53 expression level, while inhibition of p53 partially restored the suppressed cell proliferation and increased ferroptosis in ANP32E-depleted cells. Additionally, knocking out ANP32E significantly enhanced EC cell sensitivity to PTX, Combining PTX with the ferroptosis inducer erastin was more effective in inhibiting tumor growth. In vivo, we confirmed the synergistic effect of ANP32E knock-out combined with PTX demonstrating superior tumor suppressing. Overall, our findings suggest that ANP32E regulates EC progression and ferroptosis through the p53/SLC7A11 axis, offering a potential molecular target for overcoming PTX resistance in EC treatment.
Keywords: ANP32E; Esophageal cancer; Ferroptosis; P53/SLC7A11; Paclitaxel resistance.
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