ELK3-GATA3 axis modulates MDA-MB-231 metastasis by regulating cell-cell adhesion-related genes

Kim, Kwangsoo; Kim, Jiewan; Kim, Miyoung; Park, Kyung-Soon

doi:10.1016/j.bbrc.2018.03.011

Cited by 18 publications

(13 citation statements)

References 27 publications

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“…Loss of E-cadherin is considered to be an elemental event in the process of EMT, which played a vital role in cancer metastasis [23]. It was reported that the expression of E-cadherin was suppressed in GATA3-knockout MDA-MB-231 cells [24]. Our data illustrated that the expression level of E-cadherin in ZR-75-1 cells was correlated to that of GATA3.…”

Section: Discussionsupporting

confidence: 59%

Increasing of malignancy of breast cancer cells after cryopreservation: molecular detection and activation of angiogenesis after CAM-xenotransplantation

Todorov

Isachenko

et al. 2020

BMC Cancer

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Background: Ovarian tissue cryopreservation has a wide range of cancerous indications. Avoiding relapse becomes a specific concern that clinicians frequently encounter. The data about the comparative viability of cancer cells after cryopreservation are limited. This study aimed to evaluate the effect of cryopreservation on breast cancer cells. Methods: We used in-vitro cultured ZR-75-1 and MDA-MB-231 cell lines. Cell samples of each lineage were distributed into the non-intervened and cryopreserved groups. The cryopreservation procedures comprised programmed slow freezing followed by thawing at 100°C, 60 s. Biological phenotypes and the related protein markers were compared between the two groups. The EVOS FL Auto 2 Cell Image System was used to monitor cell morphology. Cell proliferation, motility, and penetration were characterized by CCK-8, wound-healing, and transmembrane assay, respectively. The expression of Ki-67, P53, GATA3, E-cadherin, Vimentin, and F-Actin was captured by immunofluorescent staining and western blotting as the proxy measurements of the related properties. The chorioallantoic membrane (CAM) xenotransplantation was conducted to explore angiogenesis induced by cancer cells. Results: After 5 days in vitro culture, the cell concentration of cryopreserved and non-intervened groups was 15.7 × 10 4 vs. 14.4 × 10 4 cells/ml, (ZR-75-1, p > 0.05), and 25.1 × 10 4 vs. 26.6 × 10 4 cells/ml (MDA-MB-231, p > 0.05). Some cryopreserved ZR-75-1 cells presented spindle shape with filopodia and lamellipodia and dissociated from the cell cluster after cryopreservation. Both cell lines demonstrated increased cell migrating capability and invasion after cryopreservation. The expression of Ki-67 and P53 did not differ between the cryopreserved and non-intervened groups. E-cadherin and GATA3 expression downregulated in the cryopreserved ZR-75-1 cells. Vimentin and F-actin exhibited an upregulated level in cryopreserved ZR-75-1 and MDA-MB-231 cells. The cryopreserved MDA-MB-231 cells induced significant angiogenesis around the grafts on CAM with the vascular density 0.313 ± 0.03 and 0.342 ± 0.04, compared with that of non-intervened cells of 0.238 ± 0.05 and 0.244 ± 0.03, p < 0.0001.

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Section: Discussionsupporting

confidence: 59%

Increasing of malignancy of breast cancer cells after cryopreservation: molecular detection and activation of angiogenesis after CAM-xenotransplantation

Todorov

Isachenko

et al. 2020

BMC Cancer

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“…Therefore, evaluation of the involved genes can be diagnostic, prognostic and therapeutic targets 22,56 . Besides, the regulatory role of GATA3 in adhesion molecules expression has been identified in cell culture analysis 57 . Hence, expression variation of these genes can happen in association with GATA3 situation induced by mutations.…”

Section: Discussionmentioning

confidence: 99%

GATA3 somatic mutations are associated with clinicopathological features and expression profile in TCGA breast cancer patients

Afzaljavan

Sadr

Savas

et al. 2021

Sci Rep

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The effect of somatic mutations and the gene expression profiles on the prognosis is well documented in cancer research. This study was conducted to evaluate the association of GATA3 somatic mutations with tumor features, survival, and expression profiles in breast cancer. Clinicopathological information was compared between TCGA-BRCA patients with GATA3-mutant and non-mutant tumors in all patients as well as in ER-positive subgroup. Cox-regression method was used to evaluate the association of the GATA3 mutation status with overall survival time. Differential gene expression, functional annotation, and protein–protein interaction analyses were performed using edgeR, Metascape, DAVID, STRING and CytoNCA. GATA3-mutant and non-mutant samples had significantly different clinicopathological features (p < 0.05). While GATA3 mutation status was not associated with the overall survival in the entire cohort (padj = 0.52), the GATA3-wild type ER-positive cases had a better prognosis than mutant ones (padj = 0.04). GATA3 expression was higher in tumors than normal tissues. Several pathways were different between mutant and non-mutant groups (p < 0.05). Interleukin-6 was found as the highest scored gene in both comparisons (normal vs. mutant and normal vs. non-mutant groups) in the entire patient and in the ER-positive subgroup, suggesting the association of IL6 with breast tumorigenesis. These findings suggest that GATA3 mutations can be associated with several tumor characteristics and influence the pattern of gene expression. However, GATA3 mutation status seems to be a prognostic factor for the disease only in ER-positive patients.

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“…Lee et al found that ELK3 expression was upregulated in CD133 + /CD44 + liver cancer stem cells, and silencing of ELK3 attenuated their metastatic potential by regulating HIF-1α expression [12]. In breast cancer, suppression of ELK3 in MDA-MB-231 cells resulted in the loss of metastatic characteristics, mainly by activating GATA binding protein 3 (GATA3) to regulate the expression of cell-cell adhesion factors and tight junctional proteins [12,19].…”

Section: Introductionmentioning

confidence: 99%

Silencing of ELK3 Induces S‐M Phase Arrest and Apoptosis and Upregulates SERPINE1 Expression Reducing Migration in Prostate Cancer Cells

Mao

Bao

et al. 2020

BioMed Research International

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ELK3, an ETS domain-containing transcription factor, participates in various physiological and pathological processes including cell proliferation, migration, angiogenesis, and malignant progression. However, the role of ELK3 in prostate cancer cells and its mechanism are not fully understood. The contribution of ELK3 to prostate cancer progression was investigated in the present study. We showed that silencing of ELK3 by siRNA in prostate cancer cell DU145 induced S-M phase arrest, promoted apoptosis, inhibited cell proliferation and migration in vitro, and suppressed xenograft growth in mice in vivo. In accordance with its ability to arrest cells in S-M phase, the expression of cyclin A and cyclin B was downregulated. In addition, the expression of p53 was upregulated following ELK3 knockdown, while that of antiapoptotic Bcl-2 was decreased. The migration inhibition may partly due to upregulation of SERPINE1 (a serine protease inhibitor) followed ELK3 knockdown. Consistently, downregulation of SERPINE1 resulted in a modest elimination of migration inhibition resulted from ELK3 knockdown. Furthermore, we found that the AKT signaling was activated in ELK3 knockdown cells, and treatment these cells with AKT inhibitor attenuated SERPINE1 expression induced by ELK3 silencing, suggesting that activation of AKT pathway may be one of the reasons for upregulation of SERPINE1 after ELK3 knockdown. In conclusion, modulation of ELK3 expression may control the progression of prostate cancer partly by regulating cell growth, apoptosis, and migration.

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ELK3-GATA3 axis modulates MDA-MB-231 metastasis by regulating cell-cell adhesion-related genes

Cited by 18 publications

References 27 publications

Increasing of malignancy of breast cancer cells after cryopreservation: molecular detection and activation of angiogenesis after CAM-xenotransplantation

Increasing of malignancy of breast cancer cells after cryopreservation: molecular detection and activation of angiogenesis after CAM-xenotransplantation

GATA3 somatic mutations are associated with clinicopathological features and expression profile in TCGA breast cancer patients

Silencing of ELK3 Induces S‐M Phase Arrest and Apoptosis and Upregulates SERPINE1 Expression Reducing Migration in Prostate Cancer Cells

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