Speckle‐type POZ protein suppresses lipid accumulation and prostate cancer growth by stabilizing fatty acid synthase

Gang, Xiaokun; Xuan, Lili; Zhao, Xue; Lv, You; Li, Fēi; Wang, Yao; Wang, Guixia

doi:10.1002/pros.23793

Cited by 20 publications

(7 citation statements)

References 19 publications

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“…Here we provide evidence that, SPOP-NANOG interaction allows SPOP to control NANOG activity and reduce its oncogenic potential in pancreatic cancer. In recently published studies, SPOP substrates such as BRD2/3/4 22 , FASN 23 , ATF2 24 , ERG 25 , AR 26 , PTEN 27 , etc., all contain the SBC degron (φ-π-S-S/T-S/T), and SPOP recognizes SBC degron to promote its multimeric ubiquitination. This provides strong evidence for further searching for new SPOP substrates in pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

SPOP suppresses pancreatic cancer progression by promoting the degradation of NANOG

Tan

et al. 2019

Cell Death Dis

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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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Section: Discussionmentioning

confidence: 99%

SPOP suppresses pancreatic cancer progression by promoting the degradation of NANOG

Tan

et al. 2019

Cell Death Dis

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“…The tumor suppressor speckle-type POZ protein is another ubiquitin ligase for FASN ubiquitylation. The speckle-type POZ protein mutants commonly found in prostate cancer cannot bind to FASN, thereby up-regulating FASN expression and lipid accumulation in prostate cancer cells ( Gang et al, 2019 ). FASN stability is also regulated by its SUMOylation, which protects FASN against proteasomal degradation in breast cancer cells ( Floris et al, 2020 ).…”

Section: Lipogenesismentioning

confidence: 99%

Lipid metabolism and cancer

Bian

Meng

et al. 2020

Journal of Experimental Medicine

510

329

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Dysregulation in lipid metabolism is among the most prominent metabolic alterations in cancer. Cancer cells harness lipid metabolism to obtain energy, components for biological membranes, and signaling molecules needed for proliferation, survival, invasion, metastasis, and response to the tumor microenvironment impact and cancer therapy. Here, we summarize and discuss current knowledge about the advances made in understanding the regulation of lipid metabolism in cancer cells and introduce different approaches that have been clinically used to disrupt lipid metabolism in cancer therapy.

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“…E3 ligase SPOP mutation, which is common in prostate cancer, inhibits its ubiquitination of FASN. Increased FASN triggers lipid accumulation and promotes prostate cancer progression [283]. AKT activation promotes deubiquitination of FASN by the USP2a and increased lipogenesis, which promotes hepatocarcinogenesis [284,285].…”

Section: Ubiquitination and Fatty Acid Metabolismmentioning

confidence: 99%

The role of ubiquitination and deubiquitination in cancer metabolism

Sun¹,

Liu²,

Yang³

2020

Mol Cancer

277

178

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Metabolic reprogramming, including enhanced biosynthesis of macromolecules, altered energy metabolism, and maintenance of redox homeostasis, is considered a hallmark of cancer, sustaining cancer cell growth. Multiple signaling pathways, transcription factors and metabolic enzymes participate in the modulation of cancer metabolism and thus, metabolic reprogramming is a highly complex process. Recent studies have observed that ubiquitination and deubiquitination are involved in the regulation of metabolic reprogramming in cancer cells. As one of the most important type of post-translational modifications, ubiquitination is a multistep enzymatic process, involved in diverse cellular biological activities. Dysregulation of ubiquitination and deubiquitination contributes to various disease, including cancer. Here, we discuss the role of ubiquitination and deubiquitination in the regulation of cancer metabolism, which is aimed at highlighting the importance of this post-translational modification in metabolic reprogramming and supporting the development of new therapeutic approaches for cancer treatment.

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Speckle‐type POZ protein suppresses lipid accumulation and prostate cancer growth by stabilizing fatty acid synthase

Cited by 20 publications

References 19 publications

SPOP suppresses pancreatic cancer progression by promoting the degradation of NANOG

SPOP suppresses pancreatic cancer progression by promoting the degradation of NANOG

Lipid metabolism and cancer

The role of ubiquitination and deubiquitination in cancer metabolism

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