NUMA1 modulates apoptosis of esophageal squamous cell carcinoma cells through regulating ASK1-JNK signaling pathway.

Esophageal squamous cell carcinoma (ESCC) is a common malignancy worldwide with a low survival rate due to a lack of therapeutic targets. Here, our results showed that nuclear mitotic apparatus protein 1 (NUMA1) transcript and protein levels are significantly upregulated in ESCC patient samples and its high expression predicated poor prognosis. Knock-down of NUMA1 promoted cell apoptosis and suppressed cell proliferation and colony formation. By using cell-derived xenograft (CDX) and patient-derived xenograft (PDX) mice models, we found silencing the NUMA1 expression suppressed tumor progression. In addition, conditional knocking-out of NUMA1 reduced 4NQO-induced carcinogenesis in mice esophagus, which further confirmed the oncogenic role of NUMA1 in ESCC. Mechanistically, from the immunoprecipitation assay we revealed that NUMA1 interacted with GSTP1 and TRAF2, promoted the association of TRAF2 with GSTP1 while inhibited the interaction of TRAF2 and ASK1, thus to regulate sustained activation of JNK. In summary, our findings suggest that NUMA1 plays an important role during ESCC progression and it functions through regulating ASK1-MKK4-SAPK/JNK signaling pathway. © 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Citation

Shuying Yin, Simin Zhao, Jian Li, Kangdong Liu, Xinli Ma, Zihan Zhang, Rui Wang, Jie Tian, Fangfang Liu, Yanming Song, Mengqiu Song, Ran Zhao, Ran Yang, Mee-Hyun Lee, Zigang Dong. NUMA1 modulates apoptosis of esophageal squamous cell carcinoma cells through regulating ASK1-JNK signaling pathway. Cellular and molecular life sciences : CMLS. 2023 Jul 18;80(8):211

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PMID: 37462735

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