Hydrogen Peroxide Enhances TGFβ-mediated Epithelial-to-Mesenchymal Transition in Human Mammary Epithelial MCF-10A Cells

Iizuka, Daisuke; Sasatani, Megumi; Barcellos-Hoff, Mary Helen; Kamiya, Kenji

doi:10.21873/anticanres.11408

Cited by 9 publications

(6 citation statements)

References 25 publications

(34 reference statements)

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“…Similarly, extracellular signal-regulated kinase (ERK) inhibition could repress TGFβ and H 2 O 2 -induced EMT, further supporting the important role of ROS in TGFβ-induced EMT via the receptor tyrosine kinase pathways [120]. In accordance, another recent finding indicated H 2 O 2 -enhanced TGFβmediated EMT via SMAD and MAPK kinase (MEK)/ERK signaling in MCF-10A human mammary epithelial cells [126] (Fig. 4).…”

Section: Redox Regulation Of Tgfβ-mediated Emtsupporting

confidence: 74%

TGFβ-induced metabolic reprogramming during epithelial-to-mesenchymal transition in cancer

Wang

Dijke

Kostidis

et al. 2019

Cell. Mol. Life Sci.

173

144

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Metastasis is the most frequent cause of death in cancer patients. Epithelial-to-mesenchymal transition (EMT) is the process in which cells lose epithelial integrity and become motile, a critical step for cancer cell invasion, drug resistance and immune evasion. The transforming growth factor-β (TGFβ) signaling pathway is a major driver of EMT. Increasing evidence demonstrates that metabolic reprogramming is a hallmark of cancer and extensive metabolic changes are observed during EMT. The aim of this review is to summarize and interconnect recent findings that illustrate how changes in glycolysis, mitochondrial, lipid and choline metabolism coincide and functionally contribute to TGFβ-induced EMT. We describe TGFβ signaling is involved in stimulating both glycolysis and mitochondrial respiration. Interestingly, the subsequent metabolic consequences for the redox state and lipid metabolism in cancer cells are found to be in favor of EMT as well. Combined we illustrate that a better understanding of the mechanistic links between TGFβ signaling, cancer metabolism and EMT holds promising strategies for cancer therapy, some of which are already actively being explored in the clinic.

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Section: Redox Regulation Of Tgfβ-mediated Emtsupporting

confidence: 74%

TGFβ-induced metabolic reprogramming during epithelial-to-mesenchymal transition in cancer

Wang

Dijke

Kostidis

et al. 2019

Cell. Mol. Life Sci.

173

144

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“…Roles of interstitial collagen and BM collagen in mammary tumor development have been determined [ 61 – 63 ]. However, function of membrane-associated collagens in breast cancer is not well studied.…”

Section: Discussionmentioning

confidence: 99%

Membrane associated collagen XIII promotes cancer metastasis and enhances anoikis resistance

et al. 2018

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BackgroundIncreased collagen expression and deposition are associated with cancer progression and poor prognosis in breast cancer patients. However, function and regulation of membrane-associated collagen in breast cancer have not been determined. Collagen XIII is a type II transmembrane protein within the collagen superfamily. Experiments in tissue culture and knockout mouse models show that collagen XIII is involved in cell adhesion and differentiation of certain cell types. In the present study, we determined roles of collagen XIII in breast cancer progression and metastasis.MethodsWe analyzed the association of collagen XIII expression with breast cancer development and metastasis using published gene expression profiles generated from human breast cancer tissues. Utilizing gain- and loss- of function approaches and 3D culture assays, we investigated roles of collagen XIII in regulating invasive tumor growth. Using the tumorsphere/mammosphere formation assay and the detachment cell culture assay, we determined whether collagen XIII enhances cancer cell stemness and induces anoikis resistance. We also inhibited collagen XIII signaling with β1 integrin function-blocking antibody. Finally, using the lung colonization assay and the orthotopic mammary tumor model, we investigated roles of collagen XIII in regulating breast cancer colonization and metastasis. Cox proportional hazard (log-rank) test, two-sided Student’s t-test (two groups) and one-way ANOVA (three or more groups) analyses were used in this study.ResultsCollagen XIII expression is significantly higher in human breast cancer tissue compared with normal mammary gland. Increased collagen XIII mRNA levels in breast cancer tissue correlated with short distant recurrence free survival. We showed that collagen XIII expression promoted invasive tumor growth in 3D culture, enhanced cancer cell stemness, and induced anoikis resistance. Collagen XIII expression induced β1 integrin activation. Blocking β1 integrin activation significantly reduced collagen XIII-induced invasion and mammosphere formation. Importantly, silencing collagen XIII in MDA-MB-231 cells reduced lung colonization and metastasis.ConclusionsOur results demonstrate a novel function of collagen XIII in promoting cancer metastasis, cell invasion, and anoikis resistance.Electronic supplementary materialThe online version of this article (10.1186/s13058-018-1030-y) contains supplementary material, which is available to authorized users.

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“…Furthermore, it is known that increased Cdh2 expression confers further migrative abilities to PCa cells and thereby increases their metastatic potential (28). Since it has been shown that oxidative stress alters E-and N-cadherin levels in pancreas and breast cancers in previous reports (20)(21)(22), we investigated the effects of the sublethal dose of H 2 O 2 , which was determined in the previous step, on E-and N-cadherin levels in PCa cells. Indeed, we have observed that H 2 O 2 induced alterations in E-and N-cadherin levels are ERK dependent.…”

Section: Discussionmentioning

confidence: 99%

“…Since the previous studies have reported that oxidative stress may cause a decrease in E-cadherin level and an increase in Ncadherin level in pancreas and breast cancers (20)(21)(22), the effects of a sublethal dose of H 2 O 2 on E-and N-cadherin protein levels were investigated in PCa cells. PC-3 and LNCaP cells were seeded on 60 mm plates and were treated with H 2 O or a 50 μM concentration of H 2 O 2 for 24 h. Total cell lysates were extracted and were used for western blotting.…”

Section: H 2 O 2 Treatment Alters E-and N-cadherin Levels In Pca Cellsmentioning

confidence: 99%

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Increased ROS alters E-/N-cadherin levels and promotes migration in prostate cancer cells

Varisli¹,

Veysel²

2022

BLL

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BACKGROUND: Increased ROS has been reported to cause a change in E-and N-cadherin levels, and consequently promotes migrative behaviors in pancreas and breast cancer cells. In this study, the effect of a sublethal dose of H 2 O 2 on E-and N-cadherin levels, and on migrative behaviors of PCa cells was investigated. METHODS: To determine a sublethal concentration of H 2 O 2 on cell proliferation and ROS production were examined using WST-1 and DCFH-DA assays, respectively. E-and N-cadherin protein and mRNA levels were investigated by western blotting and real-time PCR, respectively. The migrative potentials of the cells were examined by Cytoselect 96-well cell migration assay. RESULTS: Treatment of the PCa cells with a sublethal dose of H 2 O 2 results in a decrease in E-cadherin and an increase in N-cadherin levels, at both mRNA and protein levels. However, inhibition of ERK using PD98059 abolishes the effects of H 2 O 2 . In addition, the cells that were treated with H 2 O 2 have gained further migrative abilities compared to control cells, and this ability was repressed when PD98059 was used together with H 2 O 2 . CONCLUSION: Increased ROS alters E-and N-cadherin levels in an ERK-dependent manner and thereby promotes the migrative abilities of PCa cells (Fig. 3, Ref. 32).

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Hydrogen Peroxide Enhances TGFβ-mediated Epithelial-to-Mesenchymal Transition in Human Mammary Epithelial MCF-10A Cells

Cited by 9 publications

References 25 publications

TGFβ-induced metabolic reprogramming during epithelial-to-mesenchymal transition in cancer

TGFβ-induced metabolic reprogramming during epithelial-to-mesenchymal transition in cancer

Membrane associated collagen XIII promotes cancer metastasis and enhances anoikis resistance

Increased ROS alters E-/N-cadherin levels and promotes migration in prostate cancer cells

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