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Mol Cell Biol. 2017 Oct 27;37(22). pii: e00265-17. doi: 10.1128/MCB.00265-17. Print 2017 Nov 15.

RNF20 Suppresses Tumorigenesis by Inhibiting the SREBP1c-PTTG1 Axis in Kidney Cancer.

Author information

1
National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, Seoul, South Korea.
2
Department of Urology, Seoul National University Hospital, Seoul, South Korea.
3
Institute for Future Medicine, Samsung Medical Center, Seoul, South Korea.
4
Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, South Korea.
5
Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
6
Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea.
7
Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
8
National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, Seoul, South Korea jaebkim@snu.ac.kr.

Abstract

Elevated lipid metabolism promotes cancer cell proliferation. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancers, characterized by ectopic lipid accumulation. However, the relationship between aberrant lipid metabolism and tumorigenesis in ccRCC is not thoroughly understood. Here, we demonstrate that ring finger protein 20 (RNF20) acts as a tumor suppressor in ccRCC. RNF20 overexpression repressed lipogenesis and cell proliferation by inhibiting sterol regulatory element-binding protein 1c (SREBP1c), and SREBP1 suppression, either by knockdown or by the pharmacological inhibitor betulin, attenuated proliferation and cell cycle progression in ccRCC cells. Notably, SREBP1c regulates cell cycle progression by inducing the expression of pituitary tumor-transforming gene 1 (PTTG1), a novel target gene of SREBP1c. Furthermore, RNF20 overexpression reduced tumor growth and lipid storage in xenografts. In ccRCC patients, RNF20 downregulation and SREBP1 activation are markers of poor prognosis. Therefore, RNF20 suppresses tumorigenesis in ccRCC by inhibiting the SREBP1c-PTTG1 axis.

KEYWORDS:

PTTG1; RNF20; SREBP1c; ccRCC; tumorigenesis

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