Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, China.
Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.
Cell Death Dis. 2020 Jun 15;11(6):464. doi: 10.1038/s41419-020-2640-8.
Nuclear envelope component PRR14 has been detected to be upregulated in varieties of cancers, especially in breast cancer. But its role in breast carcinogenesis is poorly understood. In this study, we show PRR14 contributes to breast carcinogenesis mainly through overexpression, which derives from elevated transcription and gene amplification. Increased PRR14 expression promotes breast cancer cell proliferation and tumor formation. Biochemical analysis reveals, in addition to previously reported activation of PI3-kinase/Akt/mTOR pathway, PRR14 overexpression regulates cell cycle in breast cancer by inhibiting CHEK2's activation, followed with the deregulation of DNA damage pathway. In correspondence, CHEK2 and PRR14 show opposite impact on breast cancer patients receiving chemotherapy. Collectively, our study is the first to document the oncogenetic role of PRR14 in breast cancer, which protects cells from apoptosis and stimulates proliferation by activating the PI3-kinase/Akt/mTOR pathway and inhibiting the CHEK2 pathway. Both of these pathways are of great influence in breast cancer and PRR14 appears to be their novel interacting node, which renders patients more resistance to chemotherapy and provides a potential therapeutic target in breast cancer.
核包膜成分 PRR14 在多种癌症中被检测到上调，尤其是在乳腺癌中。但其在乳腺癌发生中的作用尚不清楚。在这项研究中，我们发现 PRR14 主要通过过表达促进乳腺癌发生，而过表达源于转录水平的升高和基因扩增。增加的 PRR14 表达促进乳腺癌细胞增殖和肿瘤形成。生化分析表明，除了先前报道的激活 PI3-激酶/Akt/mTOR 通路外，PRR14 过表达通过抑制 CHEK2 的激活来调节乳腺癌中的细胞周期，随后导致 DNA 损伤通路失调。相应地，CHEK2 和 PRR14 对接受化疗的乳腺癌患者的影响相反。总的来说，我们的研究首次证明了 PRR14 在乳腺癌中的致癌作用，它通过激活 PI3-激酶/Akt/mTOR 通路和抑制 CHEK2 通路来保护细胞免于凋亡并刺激增殖。这两条通路在乳腺癌中都有很大的影响，而 PRR14 似乎是它们新的相互作用节点，这使得患者对化疗的耐药性更高，并为乳腺癌提供了一个潜在的治疗靶点。
