Regulatory mechanism of tumor cell proliferation by pluripotency-associated transcriptional repressor NACC1

NACC 1的高表达与乳腺癌、卵巢癌和宫颈癌的肿瘤复发和生长相关。为了阐明NACC 1过表达促进人类恶性肿瘤生长的分子机制，我们确定了NACC 1是否调节乳腺癌细胞系中的β-连环蛋白/TCF通路。同时，进行NACC 1相互作用蛋白的蛋白质组学分析。我们鉴定了NACC 2、ZKSCAN 1和PLK 1为新的NACC 1-intracting蛋白。与非同步细胞相比，在中期同步的细胞中NACC 1-PLK 1相互作用增强。PLK 1表达和NACC 1-PLK 1共定位在中期特异性观察到，而NACC 1表达在任何细胞周期阶段观察到。此外，NACC 1磷酸化PLK 1升高中期同步化。

Elevated expression of NACC1 associates with tumor recurrence and growth of breast, ovarian and cervical cancers. To clarify the molecular mechanism of tumor growth acceleration by NACC1 overexpression in human malignancies, we determined whether NACC1 regulates beta-catenin/TCF pathway in breast cancer cell lines. In parallel, proteomic analysis of NACC1 interacting proteins was carried out. We identified NACC2, ZKSCAN1 and PLK1 as novel NACC1-intracting proteins. NACC1-PLK1 interaction was elevated in cells synchronized at metaphase compared to asynchronous cells. PLK1 expression and NACC1-PLK1 colocalization was observed specifically in metaphase, whereas NACC1 expression was observed in any cell cycle stages. In addition, NACC1 phosphorylation by PLK1 was elevated by metaphase synchronization.