Expression of sex-determining region Y-box protein 2 in breast cancer and its clinical significance

Feng, Xuesong; Lu, Mengji

doi:10.15537/smj.2017.7.19372

Cited by 11 publications

(8 citation statements)

References 36 publications

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“…We provide compelling evidence indicating that tumor cells in patient samples express OCT4, SOX2, and NANOG. These factors have already been associated with poor prognosis [39] and poor clinical survival in patients with cervical squamous cell carcinoma [40], breast cancer [41–44], esophageal [45, 46] lung [47] carcinoma and are involved in the cellular transformation towards a malignant phenotype [48–51]. The observation that these pioneer transcription factors were expressed only in the tumor component supports this conclusion.…”

Section: Discussionmentioning

confidence: 75%

Genes Involved in the Transcriptional Regulation of Pluripotency Are Expressed in Malignant Tumors of the Uterine Cervix and Can Induce Tumorigenic Capacity in a Nontumorigenic Cell Line

Ruíz

Valencia-González

Pérez-Montiel

et al. 2019

Stem Cells International

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Transcription factors OCT4, SOX2, KLF4, C-MYC, and NANOG (OSKM-N) regulate pluripotency and stemness, and their ectopic expression reprograms human and murine fibroblasts that constitute the key of regenerative medicine. To determine their contribution to cell transformation, we analyzed the gene expression profiles of these transcription factors in cervical cancer samples and found that they are preferentially expressed in the tumor component. Also, cancer stem cell-enriched cultures grown as sphere cultures showed overexpression of OSKM-N genes. Importantly, we observed that lentiviral-mediated transduction of these factors confers, to a nontumorigenic immortalized human cell line, properties of cancer stem cells as the ability to form tumors in a mouse model. When we performed a meta-analysis using microarray data from cervical cancer biopsies and normal tissues, we found that the expression of OSKM-N and some target genes allowed separating tumor and normal tissues between samples, which enhanced the importance of OSKM-N in the tumorigenesis. Finally, we analyzed and compared both transcript and protein expression profiles of these factors within a cohort of patients with cervical cancer. To our knowledge, this is the first time that the expression of OSKM-N is described to induce one of the main characteristics of the cancer stem cell, the tumorigenicity. And, more importantly, its exogenous expression in a nontumorigenic cell line is sufficient to induce a tumorigenic phenotype; furthermore, the differential expression of this transcription factor distinguishes tumor tissue and normal tissue in cervical samples.

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Section: Discussionmentioning

confidence: 75%

Genes Involved in the Transcriptional Regulation of Pluripotency Are Expressed in Malignant Tumors of the Uterine Cervix and Can Induce Tumorigenic Capacity in a Nontumorigenic Cell Line

Ruíz

Valencia-González

Pérez-Montiel

et al. 2019

Stem Cells International

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“…In breast cancers by comparison, the negative association between Sox2 and PR has been described by some authors (12,14), but was not significant in a meta-analysis (15). The negative association between Sox2 and FOXA1 has been demonstrated in human breast and lung cancers, in which Sox2 represses FOXA1 gene expression (37,38). Considering that PGR (the PR-encoding gene) is a direct ER target gene (39), and FOXA1 is a critical pioneer factor for ER (40), it can be hypothesized that Sox2 altered ER transcriptional activity in FMCs of the present study as it does in breast cancers (41).…”

Section: Discussionmentioning

confidence: 48%

Unfavorable Prognostic Effects of the Stem Cell Pluripotency Factor Sox2 in Feline Invasive Mammary Carcinomas

et al. 2021

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Background: Sex-determining Region Y (SRY)-box transcription factor-2 (Sox2) belongs to the “Yamanaka's factors,” necessary and sufficient to convert somatic cells into pluripotent stem cells. In breast cancers, Sox2 expression has been associated with poor prognosis, and resistance to therapy. The aims of this study were to determine the frequency of Sox2 positivity in feline invasive mammary carcinomas (FMCs), its relationships with other clinical-pathologic variables, and with patient outcomes.Materials and Methods: This study relies on a previously described retrospective cohort of 180 FMCs, diagnosed in female cats treated by mastectomy alone, with 2-year follow-up. Sox2 (clone SP76), Estrogen Receptor alpha (ER), Progesterone Receptor (PR), Ki-67, Human Epidermal growth factor Receptor 2 (HER2), Androgen Receptor (AR), Bcl-2, Forkhead box protein A1 (FOXA1), basal markers and FoxP3-positive regulatory T cells (Tregs) were detected by automated immunohistochemistry. Sox2 expression was quantitated as an index (percentage of neoplastic cells demonstrating a positive nuclear signal). The FMCs were considered Sox2-positive at threshold >42%.Results: Sox2 was not expressed in the normal mammary gland or in mammary hyperplasia without atypia, but was occasionally detected in atypical hyperplasia. In FMCs, the mean Sox2 index was 38 ± 30%, and 79/180 FMCs (44%) were Sox2-positive. Sox2 expression was associated with older age at diagnosis, lymphovascular invasion, high Ki-67 proliferation indexes, low PR and FOXA1 expression, and increased numbers of tumor-associated Tregs, but was not significantly associated with the clinical stage, histological types, and histological grade. By multivariate survival analysis, Sox2 was associated with poor cancer-specific survival (Hazard Ratio = 1.48, 95% confidence interval 1.04–2.11, p = 0.0292), independently of the pathologic tumor size, pathologic nodal stage, distant metastasis, and AR expression. A rare subgroup of FMCs characterized by an AR+Sox2–phenotype (19/180 cases, 11%) was associated with very favorable outcomes.Conclusion: Sox2 expression was associated with poor cancer-specific survival of female cats with invasive mammary carcinomas, as previously reported in human breast cancer, but was more commonly expressed in cats than reported in breast cancers. Sox2 showed complementarity with AR in FMC prognostication.

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“…In most cases, stemness genes promote cancer metastasis ( Lv et al, 2017 ; Baccelli et al, 2013 ; Tang et al, 2012 ; Celià-Terrassa and Kang, 2016 ). Sox2, a transcription factor involved in the regulation of embryonic development, functions as a novel regulator of cell invasion, migration, and metastasis in several cancer types ( Feng and Lu, 2017 ; Weina and Utikal, 2014 ). However, it was recently reported that REX1, an embryonic stem cell marker, inhibits liver cancer metastasis, indicating the complex functions of stemness genes in the process of cancer metastasis ( Luk et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Ascorbic Acid Inhibits Liver Cancer Growth and Metastasis in vitro and in vivo, Independent of Stemness Gene Regulation

Wan

Zhou²,

Fu³

et al. 2021

Front. Pharmacol.

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Experimental and clinical evidence has indicated that the natural product ascorbic acid (AA) is effective in preventing and treating various types of cancers. However, the effect of AA on liver cancer metastasis has not yet been reported. Cancer stem cells (CSCs) play pivotal roles in cancer metastasis. Here, we demonstrated that AA selectively inhibited the viability of both liver cancer cells and CSCs, reduced the formation of cancer cell colonies and CSC spheres, and inhibited tumor growth in vivo. Additionally, AA prevented liver cancer metastasis in a xenotransplantation model without suppressing stemness gene expression in liver CSCs. Further study indicated that AA increased the concentration of H2O2 and induced apoptosis in liver CSCs. Catalase attenuated the inhibitory effects of AA on liver CSC viability. In conclusion, AA inhibited the viability of liver CSCs and the growth and metastasis of liver cancer cells in vitro and in vivo by increasing the production of H2O2 and inducing apoptosis. Our findings provide evidence that AA exerts its anti-liver cancer efficacy in vitro and in vivo, in a manner that is independent of stemness gene regulation.

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Expression of sex-determining region Y-box protein 2 in breast cancer and its clinical significance

Cited by 11 publications

References 36 publications

Genes Involved in the Transcriptional Regulation of Pluripotency Are Expressed in Malignant Tumors of the Uterine Cervix and Can Induce Tumorigenic Capacity in a Nontumorigenic Cell Line

Genes Involved in the Transcriptional Regulation of Pluripotency Are Expressed in Malignant Tumors of the Uterine Cervix and Can Induce Tumorigenic Capacity in a Nontumorigenic Cell Line

Unfavorable Prognostic Effects of the Stem Cell Pluripotency Factor Sox2 in Feline Invasive Mammary Carcinomas

Ascorbic Acid Inhibits Liver Cancer Growth and Metastasis in vitro and in vivo, Independent of Stemness Gene Regulation

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