Sox2 promotes tamoxifen resistance in breast cancer cells

Piva, Marco; Domenici, Giacomo; Iriondo, Oihana; Rábano, Miriam; Simões, Bruno M; Comaills, Valentine; Barredo, Inmaculada; López-Ruiz, José; Zabalza, Ignacio; Kypta, Robert M.; Vivanco, María dM

doi:10.1002/emmm.201303411

Cited by 287 publications

(307 citation statements)

References 42 publications

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“…3A). Increased expression of Nanog and Sox2 was observed previously in MCF-7 cells that were selected for resistance to tamoxifen (26). Nanog and Sox2 were also overexpressed in BCSC-enriched mammosphere cultures of MDA-MB-231 cells (Fig.…”

Section: Resultssupporting

confidence: 71%

Chemotherapy triggers HIF-1–dependent glutathione synthesis and copper chelation that induces the breast cancer stem cell phenotype

Samanta

Xiang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

217

205

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Triple negative breast cancer (TNBC) accounts for 10-15% of all breast cancer but is responsible for a disproportionate share of morbidity and mortality because of its aggressive characteristics and lack of targeted therapies. Chemotherapy induces enrichment of breast cancer stem cells (BCSCs), which are responsible for tumor recurrence and metastasis. Here, we demonstrate that chemotherapy induces the expression of the cystine transporter xCT and the regulatory subunit of glutamate-cysteine ligase (GCLM) in a hypoxia-inducible factor (HIF)-1-dependent manner, leading to increased intracellular glutathione levels, which inhibit mitogenactivated protein kinase kinase (MEK) activity through copper chelation. Loss of MEK-ERK signaling causes FoxO3 nuclear translocation and transcriptional activation of the gene encoding the pluripotency factor Nanog, which is required for enrichment of BCSCs. Inhibition of xCT, GCLM, FoxO3, or Nanog blocks chemotherapy-induced enrichment of BCSCs and impairs tumor initiation. These results suggest that, in combination with chemotherapy, targeting BCSCs by inhibiting HIF-1-regulated glutathione synthesis may improve outcome in TNBC.hypoxia-inducible factor | paclitaxel | pluripotency factors | chemotherapy resistance | tumor-initiating cells

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Section: Resultssupporting

confidence: 71%

Chemotherapy triggers HIF-1–dependent glutathione synthesis and copper chelation that induces the breast cancer stem cell phenotype

Samanta

Xiang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

217

205

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“…Örneğin ERpozitif meme kanserinde östrojen uygulaması, kök/öncül hücreyle ilgili Nanog, Oct4 ve Sox2 genlerinin downregülasyonuna bağlı farklılaşmayı indükleyerek kanser kök hücre sayısını azaltabilmektedir (66). Kanser kök hücre/öncül hücrelerde tamoksifen direncinin, Wnt sinyal yolağının Sox2-bağımlı aktivasyonuyla oluşturulduğu öne sürülmektedir (67). Sox2, insan prostat DU145 kanser hücrelerinde tümör oluşumunu destekleyip, apoptozisten kurtulmayı sağlamıştır.…”

Section: Sox2'nin İlaç Direncindeki Rolü Ve Anti-apoptotik öZelliğiunclassified

Kanserde yeni bir hedef haline gelen çok yönlü Sox2 geni

Turaçlı¹,

Ekmekçi²

2016

Ege Tıp Dergisi

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ÖzSox2 proteini, farklılaşmamış erken embriyo kök hücrelerinin ve çeşitli yetişkin kök hücrelerinin gelişimi ve devamlılığının düzenlenmesinde rol oynayan bir transkripsiyon faktörüdür. Sox2, diğer pluripotensi faktörleri gibi posttranskripsiyonel ve post-translasyonel değişimlere uğramakta, böylece DNA'ya bağlanma aktivitesi değişebilmektedir. Sox2, kanser hücrelerinin çoğalması, invazyon, göç ve metastazında, tümör hücre ve kök hücre statüsünün devamında, hücresel programlama, apoptoz ve kemodirenç gelişimi gibi pek çok kanser aşamasında yer almaktadır. Bazı farklı bulgulara karşın çoğunlukla Sox2'nin kanser hücrelerinde anti-apoptotik bir faktör olarak çalıştığı konusunda uzlaşma vardır. Bu derlemede, Sox2'nin kök hücre devamlılığı, farklılaşması ve sinyal iletimindeki rollerini, bunun yanında gen çoğalmasıyla onkojenik özelliği kazanmasını ve moleküler hedef olarak kullanılma potansiyelini de kapsayan çok yönlü özelliklerini kısaca tartışacağız.Anahtar Sözcükler: Sox2, kanser. Abstract Sox2 protein is a transcription factor which is important for the maintenance and regulation of the permanence of undifferentiated embryonic and adult stem cells. Like the other pluripotency factors, Sox2 can be regulated by posttranscriptional and post-translational modifications which affect its binding ability to DNA. Sox2 involves in many cellular events in the initiation and progression of tumorigenesis such as proliferation of cancer cells, invasion

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“…Multidrug resistance (MDR) is the greatest obstacle in the systemic treatment of breast cancer; it renders the disease uncontrollable and causes high mortality (35)(36)(37)(38)(39). It is therefore of the utmost importance to find drugs that can control breast cancer and offer better results.…”

Section: B) Invasive Breast Cancer In Advanced Stagesmentioning

confidence: 99%

“…Alterations in TGFβ signaling have been involved. Cancer cells with EMT and cSC characteristics also acquire resistance through EMT or ATP-binding cassette (ABC) (29,35,39). b) Epigenetic changes.…”

Section: A) Epithelial-mesenchymal Transition (Emt)mentioning

confidence: 99%

Molecular aspects of breast cancer resistance to drugs (Review)

Calaf

Zepeda

Castillo

et al. 2015

International Journal of Oncology

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Abstract. Despite continuous advances in the knowledge of breast cancer pathophysiology, this type of neoplasia remains a leading cause of cancer-related death in women worldwide. Carcinogenesis takes a progressive course from somatic mutations, alteration of the DNA repair mechanisms, inhibition of growth suppressors, followed by cell proliferation, tissue invasion and risk of metastasis. Less than 10% of all cancers are hereditary, and in the case of breast cancer only 8%, a phenomenon linked to genetic changes in BRCA1 or BRCA2. All the other cancers can be caused by an infection (15%) or in most cases (75%) the etiology is unknown. Patients with genetic mutations in BRCA1 or BRCA2 have 30-60% likelihood of developing a second primary breast cancer and between 11 and 45% risk of ovarian cancer, HER-2/neu is overexpressed in ~30% of human breast tumors and it has a predictive role in chemotherapy and endocrine therapy.

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Sox2 promotes tamoxifen resistance in breast cancer cells

Cited by 287 publications

References 42 publications

Chemotherapy triggers HIF-1–dependent glutathione synthesis and copper chelation that induces the breast cancer stem cell phenotype

Chemotherapy triggers HIF-1–dependent glutathione synthesis and copper chelation that induces the breast cancer stem cell phenotype

Kanserde yeni bir hedef haline gelen çok yönlü Sox2 geni

Molecular aspects of breast cancer resistance to drugs (Review)

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