E-cadherin, Snail, ZEB-1, DNMT1, DNMT3A and DNMT3B expression in normal and breast cancer tissues*

Tavakolian, Shaian; Goudarzi, Hossein; Faghihloo, Ebrahim

doi:10.18388/abp.2019_2808

Cited by 13 publications

(11 citation statements)

References 44 publications

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“…Consistent with published findings ( 39 ), SLUG upregulation was associated with increased VIMENTIN ( Figure 6H , transcript; Figure 6I , protein) and decreased E-cadherin ( Figure 6H , transcript; Figure 6J , protein) levels. These results accord with previous reports of Slug and Snail transcriptional regulation of E-Cadherin ( 40 ) in breast cancer ( 41 , 42 ). Conversely, TRPC1 silencing resulted in the downregulation of SLUG and VIMENTIN , with corresponding increases in E-CADHERIN , while SNAIL levels remained unchanged ( Figure 6K ).…”

Section: Resultssupporting

confidence: 93%

Modulated TRPC1 Expression Predicts Sensitivity of Breast Cancer to Doxorubicin and Magnetic Field Therapy: Segue Towards a Precision Medicine Approach

et al. 2022

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Chemotherapy is the mainstream treatment modality for invasive breast cancer. Unfortunately, chemotherapy-associated adverse events can result in early termination of treatment. Paradoxical effects of chemotherapy are also sometimes observed, whereby prolonged exposure to high doses of chemotherapeutic agents results in malignant states resistant to chemotherapy. In this study, potential synergism between doxorubicin (DOX) and pulsed electromagnetic field (PEMF) therapy was investigated in: 1) MCF-7 and MDA-MB-231 cells in vitro; 2) MCF-7 tumors implanted onto a chicken chorioallantoic membrane (CAM) and; 3) human patient-derived and MCF-7 and MDA-MB-231 breast cancer xenografts implanted into NOD-SCID gamma (NSG) mice. In vivo, synergism was observed in patient-derived and breast cancer cell line xenograft mouse models, wherein PEMF exposure and DOX administration individually reduced tumor size and increased apoptosis and could be augmented by combined treatments. In the CAM xenograft model, DOX and PEMF exposure also synergistically reduced tumor size as well as reduced Transient Receptor Potential Canonical 1 (TRPC1) channel expression. In vitro, PEMF exposure alone impaired the survival of MCF-7 and MDA-MB-231 cells, but not that of non-malignant MCF10A breast cells; the selective vulnerability of breast cancer cells to PEMF exposure was corroborated in human tumor biopsy samples. Stable overexpression of TRPC1 enhanced the vulnerability of MCF-7 cells to both DOX and PEMF exposure and promoted proliferation, whereas TRPC1 genetic silencing reduced sensitivity to both DOX and PEMF treatments and mitigated proliferation. Chronic exposure to DOX depressed TRPC1 expression, proliferation, and responses to both PEMF exposure and DOX in a manner that was reversible upon removal of DOX. TRPC1 channel overexpression and silencing positively correlated with markers of epithelial-mesenchymal transition (EMT), including SLUG, SNAIL, VIMENTIN, and E-CADHERIN, indicating increased and decreased EMT, respectively. Finally, PEMF exposure was shown to attenuate the invasiveness of MCF-7 cells in correlation with TRPC1 expression. We thus demonstrate that the expression levels of TRPC1 consistently predicted breast cancer sensitivity to DOX and PEMF interventions and positively correlated to EMT status, providing an initial rationale for the use of PEMF-based therapies as an adjuvant to DOX chemotherapy for the treatment of breast cancers characterized by elevated TRPC1 expression levels.

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Section: Resultssupporting

confidence: 93%

Modulated TRPC1 Expression Predicts Sensitivity of Breast Cancer to Doxorubicin and Magnetic Field Therapy: Segue Towards a Precision Medicine Approach

et al. 2022

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“…6H) and protein (Fig. 6J) levels, in accordance with transcriptional inhibition of E-Cadherin by Slug and Snail (36) and reported E-cadherin modulation in breast cancer tumors (37) and cells (38).…”

Section: Trpc1 Overexpression Enhances Mcf-7 Proliferation and Emt But Attenuates Migratory Capacitysupporting

confidence: 85%

Modulated TRPC1 expression predicts sensitivity of breast cancer to doxorubicin and magnetic field therapy: segue towards a precision medicine approach

Tai

Fong

et al. 2021

Preprint

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BackgroundChemotherapy is the mainstream treatment modality for invasive breast cancer. Nonetheless, chemotherapy-associated adverse events can result in a patient terminating treatment. We show that transient receptor potential channel 1 (TRPC1) expression level predicts breast cancer sensitivity to doxorubicin (DOX) and pulsed electromagnetic field (PEMF) therapies.MethodsThe effects of PEMFs were examined with respect to: 1) the growth of MCF-7 cells in vitro; 2) MCF-7 tumors implanted into a chicken chorioallantoic membrane (CAM) model and; 3) patient-derived and MCF-7 breast cancer xenografts in mice.Potential synergisms between DOX and PEMF therapies were examined in these model systems and under conditions of TRPC1 overexpression or silencing in vitro.ResultsPEMF exposure impaired the survival of MCF-7 cells, but not that of nonmalignant MCF10A breast cells. The effects of PEMF- and DOX-therapies synergized in vitro at compromising MCF-7 cell growth. Synergism could be corroborated in vivo with patient-derived xenograft mouse models, wherein PEMF exposure alone or in combination with DOX reduced tumor size. Stable overexpression of TRPC1 enhanced the vulnerability of MCF-7 cells to both DOX and PEMF exposure and promoted proliferation, whereas chronic DOX exposure reduced TRPC1 expression, induced chemoresistance, precluded response to PEMF exposure and mitigated proliferation. Markers of metastasis including SLUG, SNAIL, VIMENTIN, and E-CADHERIN as well as invasiveness were also positively correlated with TRPC1 channel expression.ConclusionThe presented data supports a potential role of PEMF-therapy as an effective companion therapy to DOX-based chemotherapy for the treatment of breast cancers characterized by elevated TRPC1 expression levels.

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“…Its low expression in tumor tissues often indicates the tumor cells with high invasiveness [ 32 ]. According to the study performed by Tavakolian et al, the expression level of E-cadherin in BC tissue is significantly lower than that in adjacent tissues, and the expression level of E-cadherin is correlated with the survival time of BC [ 33 ]. β -Catenin is one of the downstream factors of the Wnt pathway.…”

Section: Discussionmentioning

confidence: 99%

Efficacy, Safety, and Tumor Marker Inhibition of Apatinib Combined with Conventional Chemotherapy Regimens for Patients with Advanced Triple-Negative Breast Cancer

Chen

Feng

Sheng

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Objective. Triple-negative breast cancer (TNBC) is an aggressive disease with highly invasive nature and poor outcomes. Due to the absence of specific treatment strategies for this tumor subgroup, patients with TNBC are treated with conventional therapeutics, frequently leading to systemic relapse. In this study, we sought to investigate apatinib combined with conventional chemotherapy regimens in treating patients with advanced TNBC concerning the efficacy, safety, expressions of tumor markers, and patient survival. Methods. This is a prospective study including 150 cases of advanced TNBC who were randomly arranged into a conventional group and combined group, with 75 cases per group. The patients in the conventional group were treated with conventional chemotherapy, and those in the combined group were treated with apatinib combined with conventional chemotherapy. The peripheral blood was collected from each patient, and carcinoembryonic antigen (CEA), carbohydrate antigen 153 (CA153), and carbohydrate antigen 125 (CA125) were determined. The expressions of nuclear proliferation antigen marker (Ki67), β-catenin, and E-cadherin were determined in the biopsy collected from each patient. Results. The objective remission rate (ORR) and disease control rate (DCR) (41.33% and 81.33%) in the combined group were notably higher than those in the conventional group (29.33% and 68.00%) ( P < 0.05 ). After treatment, the serum levels of CEA, CA153, and CA125 and the expressions of Ki67 and β-catenin were declined, but the expression of E-cadherin was increased in both groups; the combined group exhibited lower serum levels of CEA, CA153, and CA125, and the expressions of Ki67 and β-catenin were concurrent with a higher expression of E-cadherin than the conventional group ( P < 0.05 ). No significant difference was noted between the two groups regarding the occurrence of adverse reactions ( P > 0.05 ). Improved progression-free survival (PFS) was observed in the combined group compared to the conventional group ( P < 0.05 . Conclusion. These findings suggest that apatinib combined with conventional chemotherapy regimens confers a prolonged PFS for treating patients with advanced TNBC.

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E-cadherin, Snail, ZEB-1, DNMT1, DNMT3A and DNMT3B expression in normal and breast cancer tissues*

Cited by 13 publications

References 44 publications

Modulated TRPC1 Expression Predicts Sensitivity of Breast Cancer to Doxorubicin and Magnetic Field Therapy: Segue Towards a Precision Medicine Approach

Modulated TRPC1 Expression Predicts Sensitivity of Breast Cancer to Doxorubicin and Magnetic Field Therapy: Segue Towards a Precision Medicine Approach

Modulated TRPC1 expression predicts sensitivity of breast cancer to doxorubicin and magnetic field therapy: segue towards a precision medicine approach

Efficacy, Safety, and Tumor Marker Inhibition of Apatinib Combined with Conventional Chemotherapy Regimens for Patients with Advanced Triple-Negative Breast Cancer

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