Twist1-Mediated Adriamycin-Induced Epithelial-Mesenchymal Transition Relates to Multidrug Resistance and Invasive Potential in Breast Cancer Cells

Li, Qingquan; Xu, Junji; Wang, Wen‐Juan; Cao, Xi-Xi; Chen, Qi; Tang, Feng; Chen, Zhongqing; Liu, Xiuping; Xu, Zu-De

doi:10.1158/1078-0432.ccr-08-2372

Cited by 299 publications

(248 citation statements)

References 37 publications

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“…Although some cells in a tumor are killed by chemotherapy agents (apoptosis), the surviving cells undergo EMT which promotes not only cell survival but also cell metastasis and resistance to chemotherapy. 13 This highlights the strong need for rational, mechanism-based therapies. One approach with great potential to achieve this goal is the identification and targeting of key substances involved in EMT.…”

Section: Discussionmentioning

confidence: 99%

“…A bioassay for in vitro cell migration/invasion using Matrigel Invasion Chambers (Corning Costar, Corning, NY, USA) was performed as described previously. 13 Luciferase reporter assay. Cells at 50% confluence in 24-well plates were transfected using Fugene 6 (Roche, Indianapolis, IN, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Confocal immunofluorescence microscopy analysis using antibodies against ZO-1 (sc-10804, Santa Cruz Biotechnology) and F-actin (ab205, Abcam, Cambridge, UK) was performed as described previously. 13 EMSA. Protein extracts were prepared from MCF7 cells treated with adriamycin for 36 h. Protein extracts (30 mg) was used directly for EMSA to evaluated NF-kB activity as described previously.…”

Section: Methodsmentioning

confidence: 99%

“…Only the cells undergoing EMT showed enhanced invasion/metastasis and multidrug resistance. 13 Thus, EMT contributes to the malignant phenotypes of epithelial cancers in response to chemotherapy. Despite of these observations, however, an understanding of the precise molecular mechanisms mediating chemotherapy-induced EMT is still developing.…”

mentioning

confidence: 99%

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Involvement of NF-κB/miR-448 regulatory feedback loop in chemotherapy-induced epithelial–mesenchymal transition of breast cancer cells

et al. 2010

Cell Death Differ

165

127

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The epithelial-mesenchymal transition (EMT) induced by chemotherapeutic agents promotes malignant tumor progression; however, the mechanism underlying the drug-induced EMT remains unclear. In this study, we reported that miR-448 is the most downregulated microRNA following chemotherapy. Suppression of miR-448 correlated with EMT induction in breast cancer in vitro and in vivo. With the use of chromatin immunoprecipitation-seq analysis, we demonstrated that miR-448 suppression induces EMT by directly targeting special AT-rich sequence-binding protein-1 (SATB1) mRNA, leading to elevated levels of amphiregulin and thereby, increasing epidermal growth factor receptor (EGFR)-mediated Twist1 expression, as well as nuclear factor jB (NF-jB) activation. On the other hand, we also found that the adriamycin-activated NF-jB directly binds the promoter of miR-448 suppressing its transcription, suggesting a positive feedback loop between NF-jB and miR-448. Furthermore, all patients who received cyclophosphamide (CP), epirubicin plus taxotere/CP, epirubicin plus 5-fluorouracil chemotherapy showed miR-448 suppression, an increased SATB1, Twist1 expression and acquisition of mesenchymal phenotypes. These findings reveal an underlying regulatory pathway, in which the autoregulation between NF-jB and miR-448 is important for restrain miR-448 suppression upon chemotherapy and may have a role in the regulation of chemotherapy-induced EMT. Disruption of the NF-jB-miR-448 feedback loop during clinical treatment may improve the chemotherapy response of human breast cancers in which EMT is a critical component. Chemotherapy is a systemic treatment that destroys reproducing cells, but it cannot differentiate between normal and cancerous cells. Side effects occur when normal cells become damaged. Apart from the side effects of cancer chemotherapy, unexpected 'opposite effects' of chemotherapy, which enhance the critical steps in malignancy rather than inhibiting them, 1-3 have attracted progressively more attention, suggesting that novel strategies should be developed to reverse these opposite effects and render chemotherapy more effective.Tumor cells progress from non-invasive to malignant phenotypes via a series of critical steps that involve morphological changes referred to as the epithelial-mesenchymal transition (EMT). 4 EMT is a process originally observed during the embryonic development, in which cells lose epithelial characteristics. [5][6][7][8][9][10] With respect to the chemotherapy, recent studies have demonstrated a close link between EMT and insensitivity to chemotherapeutic agents. Hiscox et al. 11 showed increased b-catenin expression and elevated levels of transcription of b-catenin target genes known to be involved in tumor progression and EMT in the tamoxifen (TAM)-resistant MCF7 cells. Kajiyama et al. 12 identified an association between chronic paclitaxel resistance and induction of EMT in epithelial ovarian carcinomas. In addition, we previously showed that transient adriamycin treatmentinduced EMT and apoptosi...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Involvement of NF-κB/miR-448 regulatory feedback loop in chemotherapy-induced epithelial–mesenchymal transition of breast cancer cells

et al. 2010

Cell Death Differ

165

127

View full text Add to dashboard Cite

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“…Increased Twist expression is found in metastatic breast cancer and is required for EMT and breast cancer metastasis (Yang et al, 2004). Tumors undergoing EMT acquire resistance to chemotherapy (Yang et al, 2006;Cheng et al, 2007;Li et al 2009). Twist mediates EMT in breast cancer cells and enhances resistance to paclitaxel .…”

Section: Epithelial Mesenchymal Transitionmentioning

confidence: 99%

Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma: A Review

Satpute

Hazarey²,

Ahmed³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Research indicates that a small population of cancer cells is highly tumorigenic, endowed with the capacity for self-renewal, and has the ability to differentiate into cells that constitute the bulk of tumors. These cells are considered the ''drivers'' of the tumorigenic process in some tumor types, and have been named cancer stem cells (CSC). Epithelial-mesenchymal transition (EMT) appears to be involved in the process leading to the acquisition of stemness by epithelial tumor cells. Through this process, cells acquire an invasive phenotype that may contribute to tumor recurrence and metastasis. CSC have been identified in human head and neck squamous cell carcinomas (HNSCC) using markers such as CD133 and CD44 expression, and aldehyde dehydrogenase (ALDH) activity. Head and neck cancer stem cells reside primarily in perivascular niches in the invasive fronts where endothelial-cell initiated events contribute to their survival and function. Clinically, CSC enrichment has been shown to be enhanced in recurrent disease, treatment failure and metastasis. CSC represent a novel target of study given their slow growth and innate mechanisms conferring treatment resistance. Further understanding of their unique phenotype may reveal potential molecular targets to improve therapeutic and survival outcomes in patients with HNSCC. Here, we discuss the state-of-the-knowledge on the pathobiology of cancer stem cells, with a focus on the impact of these cells on head and neck tumor progression, metastasis and recurrence due to treatment failure.

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The FZD7‐TWIST1 axis is responsible for anoikis resistance and tumorigenesis in ovarian carcinoma

et al. 2019

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Frizzled family receptor 7 ( FZD 7 ), a Wnt signaling receptor, is associated with the maintenance of stem cell properties and cancer progression. FZD 7 has emerged as a potential therapeutic target because it is capable of transducing both canonical and noncanonical Wnt signals. In this study, we investigated the regulatory pathway downstream of FZD 7 and its functional roles. We found that FZD 7 expression was crucial to the maintenance of the mesenchymal phenotype, anoikis resistance, and spheroid and tumor formation in ovarian cancer (OC). We identified TWIST 1 as the crucial downstream effector of the FZD 7 pathway. TWIST 1 , a basic helix loop helix transcription factor, is known to associate with mesenchymal and cancer stem cell phenotypes. Manipulating TWIST 1 expression mimicked the functional consequences observed in the FZD 7 model, and overexpression of TWIST 1 partially rescued the functional phenotypes abolished by FZD 7 knockdown. We further proved that FZD 7 regulated TWIST 1 expression through epigenetic modifications of H3K4me3 and H3K27ac at the TWIST 1 proximal promoter. We also identified that the FZD 7 ‐ TWIST 1 axis regulates the expression of BCL 2 , a gene that controls apoptosis. Identification of this FZD 7 ‐ TWIST 1 ‐ BCL 2 pathway reaffirms the mechanism of anoikis resistance in OC. We subsequently showed that the FZD 7 ‐ TWIST 1 axis can be targeted by using a small molecule inhibitor of porcupine, an enzyme essential for secretion and functional activation of Wnts. In conclusion, our results identified that the FZD 7 ‐ TWIST 1 axis is important for tumorigenesis and anoikis resistance, and therapeutic inhibition results in cell death in OCs.

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Twist1-Mediated Adriamycin-Induced Epithelial-Mesenchymal Transition Relates to Multidrug Resistance and Invasive Potential in Breast Cancer Cells

Cited by 299 publications

References 37 publications

Involvement of NF-κB/miR-448 regulatory feedback loop in chemotherapy-induced epithelial–mesenchymal transition of breast cancer cells

Involvement of NF-κB/miR-448 regulatory feedback loop in chemotherapy-induced epithelial–mesenchymal transition of breast cancer cells

Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma: A Review

The FZD7‐TWIST1 axis is responsible for anoikis resistance and tumorigenesis in ovarian carcinoma

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