Properties and Clinical Relevance of Speckle-Type POZ Protein in Human Colorectal Cancer

Xu, Jiacheng; Wang, Feiran; Jiang, Haiyan; Jiang, Yasu; Chen, Jinpeng; Qin, Jun

doi:10.1007/s11605-015-2767-6

Cited by 27 publications

(22 citation statements)

References 40 publications

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“…In our previous study, we suggested the potential role of SPOP in progression of CRC. 13 However, the underlying mechanism remains unknown. In this study, we revealed that the tumor suppressor gene SPOP was inactivated by DNA methylation of its promoter region.…”

Section: Discussionmentioning

confidence: 99%

“…11, 12 Our previous study revealed that SPOP was significantly downregulated and the repression of SPOP promoted metastasis in colorectal cancer. 13 Notably, systematic whole-genome sequencing demonstrates that the SPOP gene is mutated in 6–15% of human prostate cancer, and functional analyses show that these are all loss-of-function mutations. 14, 15 However, there are only about 2% of colorectal cancers harboring SPOP mutation, which means the aberrant low expression level should account for the repression of SPOP function in colorectal cancer, instead of somatic mutation.…”

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confidence: 99%

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Silencing speckle-type POZ protein by promoter hypermethylation decreases cell apoptosis through upregulating Hedgehog signaling pathway in colorectal cancer

et al. 2016

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Epigenetic silencing of tumor suppressors contributes to the development and progression of colorectal cancer (CRC). We recently found that speckle-type POZ protein (SPOP) was significantly downregulated and the inactivation of SPOP promoted metastasis in CRC. This study aimed to clarify its epigenetic alteration, molecular mechanisms and clinical significance in CRC. Our results revealed that the core region of SPOP promoter was hypermethylated in CRC tissues and its methylation was correlated with poor survival. Transcription factor RXRA had a vital role in the regulation of SPOP gene. The data indicated that DNA methylation at −167 bp of the SPOP gene altered the binding affinity between transcription factor RXRA and SPOP promoter. Moreover, SPOP was found to associate with Gli2 and promoted its ubiquitination and degradation in CRC. Consequently, the expression level of Hh/Gli2 pathway-related apoptotic protein Bcl-2 was decreased and the function of resisting cell death was inhibited in CRC. It suggests that methylation status of SPOP promoter can be used as a novel epigenetic biomarker and a therapeutic target in CRC.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Silencing speckle-type POZ protein by promoter hypermethylation decreases cell apoptosis through upregulating Hedgehog signaling pathway in colorectal cancer

et al. 2016

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“…Numerous studies have explored the role of SPOP in tumorigenesis and progression in CRC. Frequent downregulation of SPOP was detected in CRC tissues compared with paired adjacent normal tissues at both the mRNA and protein levels, and this downregulation was also significantly related to clinicopathologic parameters such as poor differentiation, distant metastasis, and high TNM stage [29]. Furthermore, a decrease in SPOP expression might serve as a potent predictive factor of poor prognosis for patients with CRC according to Kaplan-Meier survival analysis.…”

Section: Colorectal Cancer (Crc)mentioning

confidence: 95%

“…Furthermore, a decrease in SPOP expression might serve as a potent predictive factor of poor prognosis for patients with CRC according to Kaplan-Meier survival analysis. In an in vitro study, overexpression of SPOP dramatically inhibited the proliferation and migration of CRC cells via upregulation of E-cadherin and downregulation of vimentin, MMP2, and MMP7, while this process was reversed by silencing of SPOP [29]. Moreover, one study also found that SPOP ablated MMP2 expression in CRC cells by suppressing the SP1 phosphorylation and nuclear translocation that was involved in the PI3K/Akt signaling pathway [101].…”

Section: Colorectal Cancer (Crc)mentioning

confidence: 98%

The emerging role of SPOP protein in tumorigenesis and cancer therapy

Song

Pan

et al. 2020

Mol Cancer

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The nuclear speckle-type pox virus and zinc finger (POZ) protein (SPOP), a representative substrate-recognition subunit of the cullin-RING E3 ligase, has been characterized to play a dual role in tumorigenesis and cancer progression. Numerous studies have determined that SPOP suppresses tumorigenesis in a variety of human malignancies such as prostate, lung, colon, gastric, and liver cancers. However, several studies revealed that SPOP exhibited oncogenic function in kidney cancer, suggesting that SPOP could exert its biological function in a cancer type-specific manner. The role of SPOP in thyroid, cervical, ovarian, bone and neurologic cancers has yet to be determined. In this review article, we describe the structure and regulation of SPOP in human cancer. Moreover, we highlight the critical role of SPOP in tumorigenesis based on three major categories: physiological evidence (animal models), pathological evidence (human cancer specimens) and biochemical evidence (downstream ubiquitin substrates). Furthermore, we note that SPOP could be a promising therapeutic target for cancer treatment.

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“…Recent research analysis found that SPOP protein was frequently mutated in some tumours, such as endometrial cancer, lung cancer and prostate cancer . Our previous studies reported that SPOP also had a similar situation in colon cancer, but it was not very clear in GC.…”

Section: Introductionmentioning

confidence: 91%

LncRNA ADAMTS9‐AS2 suppresses the proliferation of gastric cancer cells and the tumorigenicity of cancer stem cells through regulating SPOP

Wang

Tang

et al. 2020

J Cellular Molecular Medi

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| INTRODUC TI ONGastric cancer (GC) is one of the most common groups of malignancies in the world. There are one million new cases worldwide each year, mainly in developing countries, especially in China. The incidence of GC is second in various cancers in China. 1 As in recent decades in China for GC prevention and control efforts, the effect of treatment for GC has occurred great changes, but the survival rate remains poor. 2The specific mechanism of the occurrence and development of GC are still not entirely clear. In these years, many studies have confirmed that Abstract Nowadays, research on CSCs is still in an initial stage, and there are few studies reporting the successful isolation and identification of CSCs. In the present study, we attempted to isolate CSCs through cultivating the cell line MKN45 in defined serum-free medium and study the expression of stem cell markers or related proteins (Oct3/4, Sox2, Nanog and CD44) in CSCs. Moreover, immunofluorescence staining was performed to validate the stem cell markers of spheroid body-forming cells.Further experiments were used to evaluate the SPOP expression in tumorsphere cells. In addition, ADAMTS9-AS2 is a lncRNA that contributes to the genesis and development of many cancers, including gastric cancer (GC). We found ADAMTS9-AS2 functioned as an anti-oncogene and positively correlated with the expression of SPOP in GC tissues by combining bioinformatics analyses. Furthermore, we reported that ADAMTS9-AS2 regulated the expression of SPOP in GC cells and tumorsphere cells to inhibit GC progression. Together, our results demonstrated that SPOP and ADAMTS9-AS2 can be potential targets for GC treatment. K E Y W O R D S ADAMTS9-AS2, cancer stem cells, gastric cancer, Speckle-type POZ protein, tumorsphere S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Wang F, Tang C, Xu D, et al. LncRNA ADAMTS9-AS2 suppresses the proliferation of gastric cancer cells and the tumorigenicity of cancer stem cells through regulating SPOP.

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Properties and Clinical Relevance of Speckle-Type POZ Protein in Human Colorectal Cancer

Abstract: Our results suggest that SPOP plays a pivotal role in colorectal cancer (CRC) through mesenchymal-epithelial transition and MMPs, and it may be a potential therapeutic target in colorectal cancer.

Cited by 27 publications

References 40 publications

Silencing speckle-type POZ protein by promoter hypermethylation decreases cell apoptosis through upregulating Hedgehog signaling pathway in colorectal cancer

Silencing speckle-type POZ protein by promoter hypermethylation decreases cell apoptosis through upregulating Hedgehog signaling pathway in colorectal cancer

The emerging role of SPOP protein in tumorigenesis and cancer therapy

LncRNA ADAMTS9‐AS2 suppresses the proliferation of gastric cancer cells and the tumorigenicity of cancer stem cells through regulating SPOP

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