scholarly journals Aberrant ALOX5 Activation Correlates with HER2 Status and Mediates Breast Cancer Biological Activities through Multiple Mechanisms

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Xiao Zhou ◽  
Yi Jiang ◽  
Qiuyun Li ◽  
Zhen Huang ◽  
Huawei Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Biological Activities ◽  
Critical Role ◽  
Her2 Overexpression ◽  
Her2 Positive ◽  
Mesenchymal Transition ◽  
And Migration ◽  
Expression And Activity

Arachidonate lipoxygenases (ALOX) have been implicated in playing a critical role in tumorigenesis, development, and metastasis. We previously reported that ALOX12 is involved in breast cancer chemoresistance. In this study, we demonstrate that the ALOX5 activation correlates with the HER2 expression and mediates breast cancer growth and migration. We found that the ALOX5 expression and activity were upregulated in breast cancer patients, particularly in those tissues with HER2-positive. ALOX5 upregulation was also observed in HER2-positive breast cancer cells. In contrast, HER2 inhibition led to decreased expression and activity of ALOX5 but not ALOX5AP, suggesting that HER2 specifically regulates the ALOX5 expression and activity in breast cancer cells. We further demonstrated that ALOX5 is important for breast cancer biological activities with the predominant roles in growth and migration, likely through RhoA, focal adhesion, and PI3K/Akt/mTOR signaling but not epithelial mesenchymal transition (EMT). Our work is the first to report a correlation between the ALOX5 activity and HER2 overexpression in breast cancer. Our findings also highlight the therapeutic value of inhibiting ALOX5 in breast cancer, particularly those patients with the HER2 overexpression.

TIPE1 suppresses the invasion and migration of breast cancer cells and inhibits epithelial-to-mesenchymal transition primarily via the ERK signaling pathway

2019 ◽  
Vol 51 (10) ◽  
pp. 1008-1015 ◽  
Author(s):  
Shusheng Qiu ◽  
Wei Hu ◽  
Qiuhong Ma ◽  
Yi Zhao ◽  
Liang Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Western Blot ◽  
Cancer Cells ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Breast Cancer Cells ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration

Abstract Tumor necrosis factor α-induced protein 8-like-1 (TIPE1) functions as an activator or a repressor in a tumor cell type-specific manner. However, the role of TIPE1 in breast cancer, especially regarding metastasis, is unknown. In this study, we aimed to investigate the TIPE1 expression in breast cancer tissues, the biological functions, and the underlying mechanisms of TIPE1 regarding the metastatic properties of breast cancer cells. The results of immunohistochemical staining and western blot analysis indicated that TIPE1 expression was associated with tumor size and lymph node metastasis, and the expression of TIPE1 was downregulated in the tissues of patients with lymph node metastasis. Transwell and wound healing assay results showed that TIPE1 inhibited the invasive and migratory capacities of breast cancer cells. Moreover, the epithelial-mesenchymal transition (EMT) was suppressed in TIPE1-overexpressing cells, as demonstrated by western blot analysis. In addition, western blot analysis also showed that TIPE1 reduced the expression levels of MMP2 and MMP9 and decreased the phosphorylation level of ERK. These results suggested that TIPE1 might suppress the invasion and migration of breast cancer cells and inhibit EMT primarily via the ERK signaling pathway. Our findings revealed the anti-tumor metastasis role of TIPE1 in breast cancer and TIPE1 might be a new candidate prognostic indicator and a potential molecular target for the treatment of breast cancer.

scholarly journals Dysregulated connexin 43 in HER2-positive drug resistant breast cancer cells enhances proliferation and migration

Oncotarget ◽  
2017 ◽  
Vol 8 (65) ◽  
pp. 109358-109369 ◽  
Author(s):  
Elizabeth S. Yeh ◽  
Christina J. Williams ◽  
Carly Bess Williams ◽  
Ingrid V. Bonilla ◽  
Nancy Klauber-DeMore ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Connexin 43 ◽  
Breast Cancer Cells ◽  
Drug Resistant ◽  
Her2 Positive ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals MEK1 Inhibitor Combined with Irradiation Reduces Migration of Breast Cancer Cells Including miR-221 and ZEB1 EMT Marker Expression

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3760
Author(s):  
Nataša Anastasov ◽  
Elisabeth Hirmer ◽  
Marbod Klenner ◽  
Jessica Ott ◽  
Natalie Falkenberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Expression Analysis ◽  
Breast Cancer Cells ◽  
The Cancer Genome Atlas ◽  
Luminal A ◽  
Her2 Positive ◽  
Mesenchymal Transition ◽  
Marker Expression ◽  
Inhibitor Treatment

The miR-221 expression is dependent on the oncogenic RAS-RAF-MEK pathway activation and influences epithelial-to-mesenchymal transition (EMT). The Cancer Genome Atlas (TCGA) database analysis showed high gene significance for ZEB1 with EMT module analysis and miR-221 overexpression within the triple-negative breast cancer (TNBC) and HER2+ subgroups when compared to luminal A/B subgroups. EMT marker expression analysis after MEK1 (TAK-733) inhibitor treatment and irradiation was combined with miR-221 and ZEB1 expression analysis. The interaction of miR-221 overexpression with irradiation and its influence on migration, proliferation, colony formation and subsequent EMT target activation were investigated. The results revealed that MEK1 inhibitor treatment combined with irradiation could decrease the migratory potential of breast cancer cells including reduction of miR-221 and corresponding downstream ZEB1 (EMT) marker expression. The clonogenic survival assays revealed that miR-221 overexpressing SKBR3 cells were more radioresistant when compared to the control. Remarkably, the effect of miR-221 overexpression on migration in highly proliferative and highly HER2-positive SKBR3 cells remained constant even upon 8 Gy irradiation. Further, in naturally miR-221-overexpressing MDA-MB-231 cells, the proliferation and migration significantly decrease after miR-221 knockdown. This leads to the assumption that radiation alone is not reducing migration capacity of miR-221-overexpressing cells and that additional factors play an important role in this context. The miR-221/ZEB1 activity is efficiently targeted upon MEK1 inhibitor (TAK-733) treatment and when combined with irradiation treatment, significant reduction in migration of breast cancer cells was shown.

Amphiregulin regulates proliferation and migration of HER2-positive breast cancer cells

2017 ◽  
Vol 41 (2) ◽  
pp. 159-168 ◽  
Author(s):  
Hannah Schmucker ◽  
Walker M. Blanding ◽  
Julia M. Mook ◽  
Jessica F. Wade ◽  
Jang Pyo Park ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
And Migration ◽  
Proliferation And Migration ◽  
Positive Breast Cancer

scholarly journals Depletion of mitochondrial protease OMA1 alters proliferative properties and promotes metastatic growth of breast cancer cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Amita Daverey ◽  
Roman M. Levytskyy ◽  
Kimberly M. Stanke ◽  
Martonio Ponte Viana ◽  
Samantha Swenson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Metastatic Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Critical Role ◽  
Metastatic Breast ◽  
Protein Homeostasis ◽  
Mesenchymal Transition ◽  
Ductal Hyperplasia

Abstract Metastatic competence of cancer cells is influenced by many factors including metabolic alterations and changes in mitochondrial biogenesis and protein homeostasis. While it is generally accepted that mitochondria play important roles in tumorigenesis, the respective molecular events that regulate aberrant cancer cell proliferation remain to be clarified. Therefore, understanding the mechanisms underlying the role of mitochondria in cancer progression has potential implications in the development of new therapeutic strategies. We show that low expression of mitochondrial quality control protease OMA1 correlates with poor overall survival in breast cancer patients. Silencing OMA1 in vitro in patient-derived metastatic breast cancer cells isolated from the metastatic pleural effusion and atypical ductal hyperplasia mammary tumor specimens (21MT-1 and 21PT) enhances the formation of filopodia, increases cell proliferation (Ki67 expression), and induces epithelial-mesenchymal transition (EMT). Mechanistically, loss of OMA1 results in alterations in the mitochondrial protein homeostasis, as reflected by enhanced expression of canonic mitochondrial unfolded protein response genes. These changes significantly increase migratory properties in metastatic breast cancer cells, indicating that OMA1 plays a critical role in suppressing metastatic competence of breast tumors. Interestingly, these results were not observed in OMA1-depleted non-tumorigenic MCF10A mammary epithelial cells. This newly identified reduced activity/levels of OMA1 provides insights into the mechanisms leading to breast cancer development, promoting malignant progression of cancer cells and unfavorable clinical outcomes, which may represent possible prognostic markers and therapeutic targets for breast cancer treatment.

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