<scp>S</scp>ox2 targets cyclin<scp>E</scp>, p27 and survivin to regulate androgen‐independent human prostate cancer cell proliferation and apoptosis

Lin, Feng Huei; Lin, Ping; Zhao, Daqing; Chen, Y.; Xiao, Lijie; Qin, Wei; Li, D.; Chen, H.; Zhao, Baoshan; Zou, Haifeng; Zheng, Xiaodong; Yu, Xiuchong

doi:10.1111/j.1365-2184.2012.00812.x

Cited by 61 publications

(61 citation statements)

References 38 publications

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“…6C; Supplementary Fig. S1; data not shown), Ki67 positivity was not dependent on the SOX2 expression level, which is in contrast to findings in other tumor entities (11,17).…”

Section: Sox2 Modulates Csc Properties In Human Soc Cellscontrasting

confidence: 52%

“…More recently, enhanced SOX2 expression has been detected in several epithelial tumors (6,7,(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) suggesting that SOX2 also regulates tumorigenesis. On the basis of its prominent role in pluripotent stem cell stemness, SOX2 expression has been proposed as a general feature of CSCs (12,27,29,44).…”

Section: Discussionmentioning

confidence: 99%

“…In vivo PET/MRI analyses as well as histologic analyses of xenotransplanted mice confirmed larger tumor volumes from SOX2-overexpressing than control SOC cells. Because data in prostate as well as breast cancer suggested that SOX2 promotes tumorigenesis by inducing cell proliferation (11,17), we tested whether cell growth and proliferation were affected by SOX2. Surprisingly, mouse tumors derived from SOX2-overexpressing and control cells showed similar Ki67 staining.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, SOX2 expression has been shown in several tumor types such as lung (6)(7)(8)(9)(10), breast (11)(12)(13)(14), skin (15,16), prostate (17), ovarian (18,19), sinonasal (20) as well as different types of squamous carcinomas (21). However, the SOX2 expression pattern and the correlation with histopathologic status and clinical outcome are highly variable among tumors, suggesting distinct roles of SOX2 in individual tumors.…”

Section: Introductionmentioning

confidence: 99%

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SOX2 Expression Associates with Stem Cell State in Human Ovarian Carcinoma

et al. 2013

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The SRY-related HMG-box family of transcription factors member SOX2 regulates stemness and pluripotency in embryonic stem cells and plays important roles during early embryogenesis. More recently, SOX2 expression was documented in several tumor types including ovarian carcinoma, suggesting an involvement of SOX2 in regulation of cancer stem cells (CSC). Intriguingly, however, studies exploring the predictive value of SOX2 protein expression with respect to histopathologic and clinical parameters report contradictory results in individual tumors, indicating that SOX2 may play tumor-specific roles. In this report, we analyze the functional relevance of SOX2 expression in human ovarian carcinoma. We report that in human serous ovarian carcinoma (SOC) cells, SOX2 expression increases the expression of CSC markers, the potential to form tumor spheres, and the in vivo tumor-initiating capacity, while leaving cellular proliferation unaltered. Moreover, SOX2-expressing cells display enhanced apoptosis resistance in response to conventional chemotherapies and TRAIL. Hence, our data show that SOX2 associates with stem cell state in ovarian carcinoma and induction of SOX2 imposes CSC properties on SOC cells. We propose the existence of SOX2-expressing ovarian CSCs as a mechanism of tumor aggressiveness and therapy resistance in human SOC. Cancer Res; 73(17); 5544-55. Ó2013 AACR.

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“…6C; Supplementary Fig. S1; data not shown), Ki67 positivity was not dependent on the SOX2 expression level, which is in contrast to findings in other tumor entities (11,17).…”

Section: Sox2 Modulates Csc Properties In Human Soc Cellscontrasting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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SOX2 Expression Associates with Stem Cell State in Human Ovarian Carcinoma

et al. 2013

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“…In this connection, SOX2 is able to down-regulate OCT-4, but not vice versa. Moreover, several recent studies have shown that an important relationship exists between AKT pathway activation and SOX2, OCT-4, NANOG, and self-renewal capacity (33,34). In our study, SW1736 showed a constitutive expression of p-AKT, confirming the relationship between AKT and the self-renewal-related markers SOX2 and OCT4.…”

supporting

confidence: 71%

Multiple Pluripotent Stem Cell Markers in Human Anaplastic Thyroid Cancer: The Putative Upstream Role of SOX2

Carina

Zito

Pizzolanti

et al. 2013

Thyroid

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Background: Anaplastic thyroid carcinoma (ATC) is a rare and aggressive endocrine tumor with highly undifferentiated morphology. It has been suggested that cancer stem cells (CSCs) might play a central role in ATC. The objectives of this study were (i) to characterize CSCs from ex vivo ATC specimens by investigating the expression of several pluripotent stem cell markers, and (ii) to evaluate in vitro drug resistance modifications after specific CSC transcription factor switch-off. Methods: In ex vivo experiments, eight formalin-fixed, paraffin-embedded ATC specimens were analyzed by reverse-transcription and real-time quantitative PCR and immunohistochemistry. In in vitro experiments using ATC SW1736 cells, the expression levels of OCT-4, NANOG, and ABCG2 and the sensitivity to either cisplatin or doxorubicin were evaluated after silencing. Results: OCT-4, KLF4, and SOX2 transcription factors and C-KIT and THY-1 stem surface antigens showed variable up-regulation in all ATC cases. The SW1736 cell line was characterized by a high percentage of stem population (10.4 -2.1% of cells were aldehyde dehydrogenase positive) and high expression of several CSC markers (SOX2, OCT4, NANOG, C-MYC, and SSEA4). SOX2 silencing down-regulated OCT-4, NANOG, and ABCG2. SOX2 silencing sensitized SW1736 cells, causing a significant cell death increase (1.8-fold) in comparison to control cells with 10 lM cisplatin (93.9 -3.4% vs. 52.6 -9.4%, p < 0.01) and 2.7 fold with 0.5 lM doxorubicin (45.8 -9.9% vs. 17.1 -3.4% p < 0.01). ABCG2 silencing caused increased cell death with both cisplatin (74.9 -1.4%) and doxorubicin treatment (74.1 -0.1%) vs. no-target-treated cells (respectively, 45.8 -1.0% and 48.6 -1.0%, p < 0.001). Conclusions: The characterization of CSCs in ATC through the analysis of multiple pluripotent stem cell markers might be useful in identifying cells with a stem-like phenotype capable of resisting conventional chemotherapy. In addition, our data demonstrate that SOX2 switch-off through ABCG2 transporter down-regulation has a major role in overcoming CSC chemotherapy resistance.

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METTL3‐stabilized super enhancers‐lncRNA SUCLG2‐AS1 mediates the formation of a long‐range chromatin loop between enhancers and promoters of SOX2 in metastasis and radiosensitivity of nasopharyngeal carcinoma

Hu,

Wu,

Feng

et al. 2023

Clinical & Translational Med

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BackgroundSuper enhancers (SE) play pivotal roles in cell identity and diseases occur including tumorigenesis. The depletion of SE‐associated lncRNA transcripts, also known as super‐lncRNA, causes the activity of SE to be dysregulated.MethodsWe screened and identified an elevated metastasis‐associated SE‐lncRNA SUCLG2‐AS1 in nasopharyngeal carcinoma (NPC) using RNA‐sequencing, real‐time quantitative polymerase chain reaction (RT‐qPCR) and bioinformatics. Western blotting, RT‐qPCR, methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation, chromatin immunoprecipitation, RNA pull‐down and 3C (chromosome conformation capture assays) were used for mechanistic studies.ResultsSUCLG2‐AS1 was correlated with a poor prognosis. SUCLG2‐AS1 promotes NPC cell invasion and metastasis while repressing apoptosis and radiosensitivity in vitro and in vivo. Mechanistically, high SUCLG2‐AS1 expression occurred in an m6A‐dependent manner. SUCLG2‐AS1 was found to be located in the SE region of SOX2, and it regulated the expression of SOX2 via long‐range chromatin loop formation, which via mediating CTCF (transcription factor) occupied the SE and promoter region of SOX2, thus regulating the metastasis and radiosensitivity of NPC.ConclusionsTaken together, our data suggest that SUCLG2‐AS1 may serve as a novel intervention target for the clinical treatment of NPC.

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Sox2 targets cyclinE, p27 and survivin to regulate androgen‐independent human prostate cancer cell proliferation and apoptosis

Abstract: Sox2 expression is necessary for cell proliferation and evasion of apoptosis in prostate cancer cells and TGF-α could regulate Sox2 and survivin expression by activating the EGFR/PI3K/AKT pathway.

Cited by 61 publications

References 38 publications

SOX2 Expression Associates with Stem Cell State in Human Ovarian Carcinoma

SOX2 Expression Associates with Stem Cell State in Human Ovarian Carcinoma

Multiple Pluripotent Stem Cell Markers in Human Anaplastic Thyroid Cancer: The Putative Upstream Role of SOX2

METTL3‐stabilized super enhancers‐lncRNA SUCLG2‐AS1 mediates the formation of a long‐range chromatin loop between enhancers and promoters of SOX2 in metastasis and radiosensitivity of nasopharyngeal carcinoma

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