Exp Mol Med.  2017 Nov;49(11):e399. 10.1038/emm.2017.184.

Therapeutic inhibition of SGK1 suppresses colorectal cancer

Affiliations
  • 1Regeneration and Ageing Lab, School of Life Science, Shanghai University, Shanghai, China. junjiexiao@shu.edu.cn
  • 2Department of Chemistry, Qianweichang College, Innovative Drug Research Center, Shanghai University, Shanghai, China. xubin@shu.edu.cn
  • 3Department of General Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
  • 4Department of Dermatology, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
  • 5Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.

Abstract

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.


MeSH Terms

Animals
Apoptosis
Cause of Death
Cell Proliferation
Colon
Colorectal Neoplasms*
Fluorouracil
Heterografts
Humans
In Vitro Techniques
Mice
Repression, Psychology
RNA, Small Interfering
Fluorouracil
RNA, Small Interfering
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