Regeneration and Ageing Lab, School of Life Science, Shanghai University, Shanghai, China.
Department of Chemistry, Qianweichang College, Innovative Drug Research Center, Shanghai University, Shanghai, China.
Exp Mol Med. 2017 Nov 24;49(11):e399. doi: 10.1038/emm.2017.184.
Colorectal cancer (CRC) is one of the leading causes of death worldwide. Thus, the development of new therapeutic targets for CRC treatment is urgently needed. SGK1 is involved in various cellular activities, and its dysregulation can result in multiple cancers. However, little is known about its roles and associated molecular mechanisms in CRC. In present study, we found that SGK1 was highly expressed in tumor tissues compared with peri-tumor samples from CRC patients. In vitro experiments revealed that SGK1 overexpression promoted colonic tumor cell proliferation and migration and inhibited cell apoptosis induced by 5-fluorouracil (5-FU), while SGK1 shRNA and inhibitors showed the inverse effects. Using CRC xenograft mice models, we demonstrated that knockdown or therapeutic inhibition of SGK1 repressed tumor cell proliferation and tumor growth. Moreover, SGK1 inhibitors increased p27 expression and promoted p27 nuclear accumulation in colorectal cancer cells, and p27 siRNAs could attenuate the repression of CRC cell proliferation induced by SGK1 inhibitors. Collectively, SGK1 promotes colorectal cancer development via regulation of CRC cell proliferation, migration and survival. Inhibition of SGK1 represents a novel strategy for the treatment of CRC.
结直肠癌（CRC）是全球主要的死亡原因之一。因此，迫切需要开发新的 CRC 治疗的治疗靶点。SGK1 参与多种细胞活动，其失调可导致多种癌症。然而，其在 CRC 中的作用及其相关的分子机制知之甚少。在本研究中，我们发现 SGK1 在肿瘤组织中的表达明显高于 CRC 患者肿瘤旁样本。体外实验表明，SGK1 过表达促进结肠肿瘤细胞增殖和迁移，并抑制 5-氟尿嘧啶（5-FU）诱导的细胞凋亡，而 SGK1 shRNA 和抑制剂则显示出相反的作用。利用 CRC 异种移植小鼠模型，我们证明了 SGK1 的敲低或治疗性抑制抑制了肿瘤细胞的增殖和肿瘤生长。此外，SGK1 抑制剂增加了 p27 的表达，并促进了 p27 在结直肠癌细胞中的核积累，而 p27 siRNAs 可以减弱 SGK1 抑制剂对 CRC 细胞增殖的抑制作用。综上所述，SGK1 通过调节 CRC 细胞的增殖、迁移和存活来促进结直肠癌的发展。抑制 SGK1 可能是治疗 CRC 的一种新策略。
