Department of Urology, Shanghai Tenth People's Hospital, Tongji University, 200072, Shanghai, China.
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, 200241, Shanghai, China.
Cell Death Dis. 2018 May 24;9(6):627. doi: 10.1038/s41419-018-0646-2.
Renal cell carcinoma (RCC) is the most common malignant disease of kidney in adults. The proteasome activator REGγ was previously reported to promote the degradation of multiple important regulatory proteins and involved in the progression and development of numerous human cancers. Here, we first reported that REGγ was upregulated in RCC and its upregulation was correlated with a poor prognosis in RCC patients. REGγ depletion obviously suppressed RCC cells proliferation in vitro and in vivo. Notably, casein kinase 1ε (CK1ε) was identified as a novel target of REGγ and knockdown of CK1ε effectively abolished the effect of REGγ depletion on RCC cells growth. Importantly, we also observed that REGγ depletion activated Hippo signaling pathway via stabilizing CK1ε in RCC, indicating the cross-talk between REGγ/CK1ε axis and Hippo pathway during RCC development. In conclusion, our findings suggested that REGγ played a pivotal role in the development of RCC and maybe helpful to identify new therapeutic strategies in the treatment of RCC.
肾细胞癌（RCC）是成人肾脏最常见的恶性疾病。蛋白酶体激活剂 REGγ 先前被报道能促进多种重要调节蛋白的降解，并参与多种人类癌症的进展和发展。在这里，我们首次报道 REGγ 在 RCC 中上调，其上调与 RCC 患者的预后不良相关。REGγ 耗竭明显抑制了体外和体内 RCC 细胞的增殖。值得注意的是，酪蛋白激酶 1ε（CK1ε）被鉴定为 REGγ 的一个新靶标，CK1ε 的敲低有效地消除了 REGγ 耗竭对 RCC 细胞生长的影响。重要的是，我们还观察到 REGγ 耗竭通过稳定 RCC 中的 CK1ε 激活 Hippo 信号通路，表明在 RCC 发展过程中 REGγ/CK1ε 轴和 Hippo 通路之间存在串扰。总之，我们的研究结果表明，REGγ 在 RCC 的发展中起着关键作用，这可能有助于确定治疗 RCC 的新治疗策略。
