SPOP suppresses pancreatic cancer progression by promoting the degradation of NANOG

Cell Death Dis. 2019 Oct 17;10(11):794. doi: 10.1038/s41419-019-2017-z.

Peng Tan ¹ ², Yunke Xu ¹ ³, Yichao Du ¹ ², Lile Wu ¹, Bing Guo ¹, Shiyao Huang ², Jinhui Zhu ⁴, Bo Li ⁵, Fujun Lin ⁶, Lei Yao ⁷ ⁸

Affiliations

1 Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, 646000, Luzhou, Sichuan, China.
2 Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, 646000, Luzhou, Sichuan, China.
3 Department of Hepatobiliary Surgery, Hospital (TCM) Affiliated to Southwest Medical University, 646000, Luzhou, Sichuan, China.
4 Department of General Surgery and Laparoscopic Center, The Second Affiliated Hospital Zhejiang University School of Medicine, 310009, Hangzhou, China.
5 Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, 646000, Luzhou, Sichuan, China. liboer2002@126.com.
6 Renal Division, Department of Internal Medicine, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200092, Shanghai, China. linfujun@xinhuamed.com.cn.
7 Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, 646000, Luzhou, Sichuan, China. Yaolei2009@gmail.com.
8 Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, 646000, Luzhou, Sichuan, China. Yaolei2009@gmail.com.

PMID: 31624231 DOI: 10.1038/s41419-019-2017-z

Abstract

Speckle-type POZ domain protein (SPOP), an adaptor in the E3 ubiquitin Ligase complex, recognizes substrates and promotes protein degradation via the ubiquitin-proteasome system. It appears to help regulate progression of several cancers, and we show here that it acts as a tumor suppressor in pancreatic Cancer. Our analysis of patient tissues showed decreased SPOP expression, which was associated with poor prognosis. SPOP knockdown in SW1990 (in vitro/vivo) and PANC-1 (in vitro) cells led to significantly greater proliferation, migration, and invasion. Co-immunoprecipitation experiments in SW1990 cells showed that SPOP interacted with the stem-cell marker NANOG, and this interaction has recently been shown to play a critical role in regulating progression of prostate Cancer. We showed that, in one patient with pancreatic Cancer, the expression of a truncated form of SPOP (p.Q360*) lacking the nuclear localization signal led to nuclear accumulation of NANOG, which promoted growth and metastasis of pancreatic Cancer cells. Our results suggest that SPOP suppresses progression of pancreatic Cancer by promoting the ubiquitination and subsequent degradation of NANOG. These results identify the SPOP-NANOG interaction as a potential therapeutic target against pancreatic Cancer.

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