Snail/beta-catenin signaling protects breast cancer cells from hypoxia attack

Scherbakov, Alexander M.; Стефанова, Л Б; Sorokin, Danila V.; Semina, Svetlana E.; Berstein, Lev M.; Красильников, М. А.

doi:10.1016/j.yexcr.2013.08.019

Cited by 22 publications

(13 citation statements)

References 43 publications

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“…An important share of hypoxia‐related cell response consists in the stimulation of EMT, characterized by cellular and molecular changes that include loss of cell‐to‐cell adhesion, acquisition of a more prominent spindle‐like morphology and increased cell motility . Here we demonstrated that, only in BT‐474 cells, hypoxia induced a loss of the epithelial marker E‐cadherin, that was partially neutralized when the concomitant down‐modulation of PLC‐β2 was counteracted.…”

Section: Discussionmentioning

confidence: 63%

“…Also in breast cancer, hypoxia seems to induce both the EMT process and a stem cell‐like phenotype by activating HIF‐1α that, under reduced oxygen, is protected from ubiquination and proteasomal degradation, translocates to the nucleus and acts as transcription factor . HIF‐1α mediates hypoxia‐induced EMT via up‐regulation of transcription effectors resulting in the suppression of E‐cadherin and in the over‐expression of Vimentin . The activation of the HIF‐1α also results in the modulation of genes that regulate stem cell maintenance and, in breast tumors, the hypoxic response includes the expansion of the sub‐population of cells positive for CD133, whose gene is a direct target of this transcription factor .…”

Section: Discussionmentioning

confidence: 99%

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PLC‐β2 is modulated by low oxygen availability in breast tumor cells and plays a phenotype dependent role in their hypoxia‐related malignant potential

Brugnoli

Grassilli

Al-Qassab

et al. 2016

Molecular Carcinogenesis

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Limited oxygen availability plays a critical role in the malignant progression of breast cancer by orchestrating a complex modulation of the gene transcription largely dependent on the tumor phenotype. Invasive breast tumors belonging to different molecular subtypes are characterized by over-expression of PLC-β2, whose amount positively correlates with the malignant evolution of breast neoplasia and supports the invasive potential of breast tumor cells. Here we report that hypoxia modulates the expression of PLC-β2 in breast tumor cells in a phenotype-related manner, since a decrease of the protein was observed in the BT-474 and MCF7 cell lines while an increase was revealed in MDA-MB-231 cells as a consequence of low oxygen availability. Under hypoxia, the down-modulation of PLC-β2 was mainly correlated with the decrease of the EMT marker E-cadherin in the BT-474 cells and with the up-regulation of the stem cell marker CD133 in MCF7 cells. The increase of PLC-β2 induced by low oxygen in MDA-MB-231 cells supports the hypoxia-related reorganization of actin cytoskeleton and sustains invasion capability. In all examined cell lines, but with an opposite role in the ER-positive and ER-negative cells, PLC-β2 was involved in the hypoxia-induced increase of HIF-1α, known to affect both EMT and CD133 expression. Our data include PLC-β2 in the complex and interconnected signaling pathways induced by low oxygen availability in breast tumor cells and suggest that the forced modulation of PLC-β2 programmed on the basis of tumor phenotype may prevent the malignant progression of breast neoplasia as a consequence of intra-tumoral hypoxia. © 2016 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

PLC‐β2 is modulated by low oxygen availability in breast tumor cells and plays a phenotype dependent role in their hypoxia‐related malignant potential

Brugnoli

Grassilli

Al-Qassab

et al. 2016

Molecular Carcinogenesis

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“…Scherbakov et al . have shown that breast cancer cells can resist hypoxia through the SNAI1/beta‐catenin signal pathway . Nevertheless, in this study, we substantiated that the downregulation of SNAI1 leads to cells stagnating in the G0/G1 phase by using flow cytometry.…”

Section: Discussionmentioning

confidence: 44%

SNAI1 promotes the development of HCC through the enhancement of proliferation and inhibition of apoptosis

Bian

et al. 2016

FEBS Open Bio

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SNAI 1, a zinc‐finger transcription factor, plays an important role in the induction of epithelial–mesenchymal transition ( EMT ) in various cancers. However, the possible functions of SNAI 1 in the proliferation and apoptosis of hepatocellular carcinoma have not been clearly identified. In this study, we investigated the effects and mechanisms of SNAI 1 in the proliferation and apoptosis of hepatocellular carcinoma using clinical samples and cell lines. We found that SNAI 1 is highly expressed in the tissues of liver cancer compared with adjacent nontumor tissues. SNAI 1 is also highly expressed in the hepatoma cell lines HepG2, SMMC ‐7721, and BEL ‐7402 compared with the human normal liver cell line L02. We also observed that SNAI 1 expression was correlated with distal metastasis, incomplete tumor capsule formation, and histological differentiation in hepatocellular carcinoma ( HCC ). Moreover, we demonstrated that knockdown of SNAI 1 via lentiviral vectors of RNA i against SNAI inhibited cell proliferation by inducing G1 arrest, which was accompanied by the downregulation of cyclin D1 but not that of cyclin A. In addition, knockdown of SNAI 1 promoted apoptosis by decreasing the expression of Bcl‐2. In conclusion, our findings revealed that SNAI 1 is involved in the development of hepatocellular carcinoma via regulating the growth and apoptosis of tumor cells.

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“…It has long been known that Wnt pathway-activating mutations occur in numerous tumor types, most notably colorectal cancer [58]. More recently, interactions between HIF-1 and β-catenin identified in a variety of cancers under hypoxic conditions have been found to promote tumor cell protection, progression, and metastatic potential [59], [60], [61], amplifying the interest in Wnt signaling as a therapeutic target for cancer [62], [63], [64].…”

Section: Discussionmentioning

confidence: 99%

Wnt Pathway Activation Increases Hypoxia Tolerance during Development

et al. 2014

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Adaptation to hypoxia, defined as a condition of inadequate oxygen supply, has enabled humans to successfully colonize high altitude regions. The mechanisms attempted by organisms to cope with short-term hypoxia include increased ATP production via anaerobic respiration and stabilization of Hypoxia Inducible Factor 1α (HIF-1α). However, less is known about the means through which populations adapt to chronic hypoxia during the process of development within a life time or over generations. Here we show that signaling via the highly conserved Wnt pathway impacts the ability of Drosophila melanogaster to complete its life cycle under hypoxia. We identify this pathway through analyses of genome sequencing and gene expression of a Drosophila melanogaster population adapted over >180 generations to tolerate a concentration of 3.5–4% O2 in air. We then show that genetic activation of the Wnt canonical pathway leads to increased rates of adult eclosion in low O2. Our results indicate that a previously unsuspected major developmental pathway, Wnt, plays a significant role in hypoxia tolerance.

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Snail/beta-catenin signaling protects breast cancer cells from hypoxia attack

Cited by 22 publications

References 43 publications

PLC‐β2 is modulated by low oxygen availability in breast tumor cells and plays a phenotype dependent role in their hypoxia‐related malignant potential

PLC‐β2 is modulated by low oxygen availability in breast tumor cells and plays a phenotype dependent role in their hypoxia‐related malignant potential

SNAI1 promotes the development of HCC through the enhancement of proliferation and inhibition of apoptosis

Wnt Pathway Activation Increases Hypoxia Tolerance during Development

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