Speckle-type POZ protein suppresses hepatocellular carcinoma cell migration and invasion via ubiquitin-dependent proteolysis of SUMO1/sentrin specific peptidase 7

Journal Article · Sun Jul 15 04:00:00 EDT 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.05.115· OSTI ID:23105757

Ji, Piyou ^[1]; Liang, Shaohua ^[2]; Li, Pengtao ^[1]; Xie, Chengrong; Li, Jie ^[3]; others, and

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1. Department of Hepatobiliary Surgery, School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, 350108 (China)
2. Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, 350108 (China)
3. Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen Translational Medical Key Laboratory of Hepatobiliary and Pancreatic Tumor, Zhongshan Hospital Xiamen University, Xiamen, 361004 (China)

Highlights: • SPOP expression was significantly downregulated in HCC and was associated with tumor size, differentiation and metastasis. • Low SPOP expression was a risk factor related to the prognosis of HCC patients. • SPOP inhibited HCC metastasis through interacting with SENP7 and promoting its degradation. Hepatocellular carcinoma (HCC) is associated with high metastatic potential and high mortality. Accumulating evidence has demonstrated that speckle-type POZ protein (SPOP) is a key adaptor molecule of ubiquitination. However, the molecular mechanism of SPOP-mediated ubiquitination in HCC metastasis remains obscure. In the present study, our results indicated that SPOP expression was significantly downregulated in HCC and was associated with tumor size, differentiation and metastasis. Cox regression model showed that low SPOP expression was a risk factor related to the prognosis of HCC patients. Loss- and gain-of-function assays demonstrated that SPOP inhibited HCC cell migration and invasion in vitro. Mechanisitically, co-immunoprecipitation and ubiquitination assays revealed that SPOP recognized and bound SENP7 and promoted its degradation via ubiquitin-dependent proteolysis. Analysis of immunohistochemistry showed that vimentin expression was correlated negatively with SPOP and positively with SENP7. These results implied that increased degradation of SENP7 by overexpression of SPOP decreased vimentin levels, which in turn attenuated HCC cell metastasis. Moreover, in vivo assays showed that SPOP overexpression also significantly suppressed liver and lung metastases. In summary, SPOP inhibits HCC cell metastasis via ubiquitin-dependent SENP7 proteolysis and may thus serve as a new opinion for the prevention of HCC metastasis.

• OSTI ID: 23105757
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 502; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
HEPATOMAS
LIVER
LUNGS
METASTASES
PROTEOLYSIS