scholarly journals Hypoxia-Induced TPM2 Methylation is Associated with Chemoresistance and Poor Prognosis in Breast Cancer

2018 ◽  
Vol 45 (2) ◽  
pp. 692-705 ◽  
Author(s):  
Jinfeng Zhang ◽  
Jian Zhang ◽  
Shouping Xu ◽  
Xianyu Zhang ◽  
Peiyuan Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Critical Role ◽  
Methylation Status ◽  
Matrix Metalloproteinase 2 ◽  
Migration And Invasion ◽  
Breast Cancer Patients ◽  
Gene Target ◽  
Node Metastasis

Background/Aims: Tropomyosin-2 (TPM2) plays important roles in functions of the cytoskeleton, such as cytokinesis, vesicle transport, cell proliferation, migration and apoptosis,and these functions imply that TPM2 also plays a role in cancer development. Indeed, it has been shown that TPM2 plays a critical role in some cancers. However, the role of TPM2 in breast cancer is still poorly characterized. Thus, we explored the role of TPM2 in breast cancer. Methods: We analysed TPM2 expression and its correlation with the clinicopathological features in breast cancer. Then, we examined the influence of hypoxia on TPM2 expression and methylation status using bisulfite sequencing PCR. Furthermore, we performed TPM2-mediated migration and invasion assays in the context of hypoxia and examined changes in matrix metalloproteinase-2 (MMP2) expression. Finally, we detected the influence of TPM2 on survival and chemotherapy drug sensitivity. Results: We found that TPM2 expression is down-regulated in breast cancer cells compared to that in normal breast cells. The data from TCGA supported these results. Promoter methylation of TPM2, which could be induced by hypoxia, was responsible for its low expression. Hypoxia might regulate cell invasiveness partly by TPM2 down-regulation-mediated changes of MMP2 expression. Importantly, low TPM2 expression was correlated with lymph node metastasis (P=0.031), tumour node metastasis stage (P=0.01), histological grade (P=0.037), and shorter overall survival (P=0.028). Univariate and multivariate analyses indicated that TPM2 was an independent predictor in breast cancer patients. Paclitaxel chemotherapy did not benefit patients with low TPM2 expression (P<0.0001). TPM2 knockdown significantly reduced cell sensitivity to paclitaxel. Conclusion: TPM2 is a potential novel tumour suppressor gene in breast cancer. TPM2 is associated with poor survival and chemoresistance to paclitaxel in breast cancer, and TPM2 may represent a promising therapeutic gene target for breast cancer patients with chemoresistance.

scholarly journals CXCR2: A Novel Mediator of Mammary Tumor Bone Metastasis

2019 ◽  
Vol 20 (5) ◽  
pp. 1237 ◽  
Author(s):  
Bhawna Sharma ◽  
Kalyan Nannuru ◽  
Sugandha Saxena ◽  
Michelle Varney ◽  
Rakesh Singh
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Mammary Tumor ◽  
Critical Role ◽  
Breast Cancer Patients ◽  
Mammary Tumor Cell ◽  
Primary Tumors

Most breast cancer patients die due to bone metastasis. Although metastasis accounts for 5% of the breast cancer cases, it is responsible for most of the deaths. Sometimes even before the detection of a primary tumor, most of the patients have bone and lymph node metastasis. Moreover, at the time of death, breast cancer patients have the bulk of the tumor burden in their bones. Therapy options are available for the treatment of primary tumors, but there are minimal options for treating breast cancer patients who have bone metastasis. C-X-C motif chemokine receptor type 2 (CXCR2) receptor-mediated signaling has been shown to play a critical role during bone-related inflammations and its ligands C-X-C motif chemokine ligand 6 (CXCL6) and 8 (CXCL8) aid in the resorption of bone during bone metastasis. In this study, we tested the hypothesis that CXCR2 contributes to mammary tumor-induced osteolysis and bone metastasis. In the present study, we examined the role of both tumor cell-derived and host-derived CXCR2 in influencing mammary tumor cell bone metastasis. For understanding the role of tumor cell-derived CXCR2, we utilized Cl66 CXCR2 knockdown (Cl66-shCXCR2) and Cl66-Control cells (Cl66-Control) and observed a significant decrease in tumor growth and tumor-induced osteolysis in Cl66-shCXCR2 cells in comparison with the Cl66-Control cells. Next, for understanding the role of host-derived CXCR2, we utilized mice with genomic knockdown of CXCR2 (Cxcr2−/−) and injected Cl66-Luciferase (Cl66-Luc) or 4T1-Luciferase (4T1-Luc) cells. We observed decreased bone destruction and metastasis in the bone of Cxcr2−/− mice. Our data suggest the importance of both tumor cell- and host-derived CXCR2 signaling in the bone metastasis of breast cancer cells.

scholarly journals Downregulation of miR-142-3p Contributes to Breast Cancer Oncogenesis

2019 ◽  
pp. 1-6
Author(s):  
Gangping WANG ◽  
Gangping WANG ◽  
Huifang Shi ◽  
Jingjing Li ◽  
Lei Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Viability ◽  
Cancer Patients ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Migration And Invasion ◽  
Breast Cancer Patients ◽  
Node Metastasis

Breast cancer is one of the commonly-encountered malignant tumors, and its morbidity is on the rise year by year. A better understanding of the molecular mechanisms of breast cancer is important. This can improve the prevention, diagnosis, and treatment.The miR-142‐3p has been shown to inhibit carcinogenesis by regulating various cellular processes, including cell cycle progression, cell migration, apoptosis, and invasion. We surgically recruited 96 breast cancer patients and the breast cancer samples, each with matched adjacent normal breast tissue were obtained, MDA-MB-231 and MCF-7 cells were cultured for experiments in vitro and measured the expression of miR‐142‐3p via quantitative real‐time polymerase chain reaction (qRT‐PCR). Cell viability, apoptosis, migration, and invasion were determined by MTT, flow cytometry, and trans-well assays. The expression of miR-142-3p was down-regulated in both cancer cell lines and cancer specimens. The reduced expression of miR-142‐3p was associated with tumor size, lymph node metastasis, and tumor-node-metastasis (TNM) stage of patients (p<0.05). However, there was no significant correlation between miR‐142‐3p expression in tumor tissues with age at diagnosis (p>0.05). Overexpression of miR-142-3p repressed cell viability, migration, and invasion, while it induced apoptosis, whereas its depletion promoted it. The results suggest miR‐142‐3p acts as a tumor suppressor and can act as a novel target for the treatment of breast cancer. Thus, restoration of miR‐142‐3p expression, for example, via miRNA replacement therapy, may represent an effective strategy for the treatment of breast cancer patients

scholarly journals Clinical impact of PTEN methylation status as a prognostic marker for breast cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Amal Ramadan ◽  
Maha Hashim ◽  
Amr Abouzid ◽  
Menha Swellam
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Markers ◽  
Prognostic Marker ◽  
Methylation Status ◽  
Clinical Impact ◽  
Breast Cancer Patients ◽  
Duct Carcinoma ◽  
Cancer Group ◽  
And Control

Abstract Background Aberrant DNA methylation of phosphatase and tensin homolog (PTEN) gene has been found in many cancers. The object of this study was to evaluate the clinical impact of PTEN methylation as a prognostic marker in breast cancer. The study includes 153 newly diagnosed females, and they were divided according to their clinical diagnosis into breast cancer patients (n = 112) and females with benign breast lesion (n = 41). A group of healthy individuals (n = 25) were recruited as control individuals. Breast cancer patients were categorized into early stage (0–I, n = 48) and late stage (II–III, n = 64), and graded into low grade (I–II, n = 42) and high grade (III, n = 70). Their pathological types were invasive duct carcinoma (IDC) (n = 66) and duct carcinoma in situ (DCI) (n = 46). Tumor markers (CEA and CA15.3) were detected using ELISA. DNA was taken away from the blood, and the PTEN promoter methylation level was evaluated using the EpiTect Methyl II PCR method. Results The findings revealed the superiority of PTEN methylation status as a good discriminator of the cancer group from the other two groups (benign and control) with its highest AUC and increased sensitivity (96.4%) and specificity (100%) over tumor markers (50% and 84% for CEA and 49.1% and 86.4% for CA15.3), respectively. The frequency of PTEN methylation was 96.4% of breast cancer patients and none of the benign and controls showed PTEN methylation and the means of PTEN methylation (87 ± 0.6) were significantly increased in blood samples of breast cancer group as compared to both benign and control groups (25 ± 0.7 and 12.6 ± 0.3), respectively. Methylation levels of PTEN were higher in the blood of patients with ER-positive than in patients with ER-negative cancers (P = 0.007) and in HER2 positive vs. HER2 negative tumors (P = 0.001). The Kaplan-Meier analysis recognizes PTEN methylation status as a significant forecaster of bad progression-free survival (PFS) and overall survival (OS), after 40 months follow-up. Conclusions PETN methylation could be supposed as one of the epigenetic aspects influencing the breast cancer prognosis that might foretell more aggressive actions and worse results in breast cancer patients.

Role of integrative medicine in the continuum of care of breast cancer patients in the Indian context

2021 ◽  
Author(s):  
Partha Basu ◽  
Richa Tripathi ◽  
Ravi Mehrotra ◽  
Koninika Ray ◽  
Anurag Srivastava ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Integrative Medicine ◽  
Continuum Of Care ◽  
Breast Cancer Patients ◽  
Indian Context ◽  
The Continuum

scholarly journals The HIF target MAFF promotes tumor invasion and metastasis through IL11 and STAT3 signaling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eui Jung Moon ◽  
Stephano S. Mello ◽  
Caiyun G. Li ◽  
Jen-Tsan Chi ◽  
Kaushik Thakkar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Invasion ◽  
Critical Role ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Invasion And Metastasis ◽  
Stat3 Signaling ◽  
Inducible Genes ◽  
Transcriptional Target

AbstractHypoxia plays a critical role in tumor progression including invasion and metastasis. To determine critical genes regulated by hypoxia that promote invasion and metastasis, we screen fifty hypoxia inducible genes for their effects on invasion. In this study, we identify v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (MAFF) as a potent regulator of tumor invasion without affecting cell viability. MAFF expression is elevated in metastatic breast cancer patients and is specifically correlated with hypoxic tumors. Combined ChIP- and RNA-sequencing identifies IL11 as a direct transcriptional target of the heterodimer between MAFF and BACH1, which leads to activation of STAT3 signaling. Inhibition of IL11 results in similar levels of metastatic suppression as inhibition of MAFF. This study demonstrates the oncogenic role of MAFF as an activator of the IL11/STAT3 pathways in breast cancer.

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