scholarly journals CYC1 Predicts Poor Prognosis in Patients with Breast Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Yingyan Han ◽  
Shujuan Sun ◽  
Meisong Zhao ◽  
Zeyu Zhang ◽  
Song Gong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Complex Iii ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Mitochondrial Complex ◽  
Online Databases ◽  
Tumor Tissues ◽  
Future Patient

Cytochrome c-1 (CYC1) is an important subunit of mitochondrial complex III. However, its role in tumor progression is unclear. We found that CYC1 was upregulated in breast tumor tissues, especially in tissues with lymph node metastasis. And higher expression of CYC1 correlates with poor prognosis in breast cancer patients using online databases and tools. Then we confirmed that CYC1 contributed to metastasis and proliferation in two highly metastatic human breast cancer cell lines. Digging into the biological function of CYC1, we found the activity of mitochondrial complex III decreased due to silencing CYC1. Then the ratio of AMP to ATP increased and AMPK was activated. Analyzing units of other mitochondrial complexes, we did not find knockdown of CYC1 expression reduced expression of any other unit of OXPHOS. We concluded that CYC1 promoted tumor metastasis via suppressing activation of AMPK and contributed to tumor growth via facilitating production of ATP. Our results indicated that CYC1 plays crucial roles in breast cancer progression and might be a predictive factor assisting future patient diagnosis.

scholarly journals IQGAP3 Overexpression Correlates With Poor Prognosis and Radiation Therapy Resistance in Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Xin Hua ◽  
Zhi-Qing Long ◽  
Ling Guo ◽  
Wen Wen ◽  
Xin Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Cancer Patients ◽  
Cell Lines ◽  
Breast Cancer Cell ◽  
Subgroup Analysis ◽  
Poor Prognosis ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Tumor Tissues

Background: IQ motif-containing GTPase activating protein 3 (IQGAP3), the latest identified member of the IQGAP family, may act as a crucial factor in cancer development and progression; however, its clinical value in breast cancer remains unestablished. We explored the correlation between IQGAP3 expression profile and the clinicopathological features in breast cancer.Methods: IQGAP3 mRNA and protein levels were detected in breast cancer cell lines and tumor tissues by real-time PCR and western blotting and compared to the normal control groups. Protein expression of IQGAP3 was also evaluated immunohistochemically in archived paraffin-embedded specimens from 257 breast cancer patients, and the associations between IQGAP3 expression level, clinical characteristics, and prognosis were analyzed. We assessed the relationship between IQGAP3 expression and sensitivity to radiation therapy which was determined by subgroup analysis.Results: IQGAP3 was significantly upregulated in breast cancer cell lines and human tumor tissues at both the mRNA and protein level compared to controls. Additionally, high levels of IQGAP3 expression were detected in 110/257 (42.8%) of archived paraffin-embedded breast cancer specimens. High IQGAP3 expression level was significantly related to clinical stage (p = 0.001), T category (p = 0.002), N category (p = 0.001), locoregional recurrence (p = 0.002), distant metastasis (p = 0.001), and vital status (p = 0.001). Univariate and multivariate statistical analysis showed that IQGAP3 expression was an independent prognostic factor among all 257 breast cancer patients in our cohort (p = 0.003, p = 0.001). Subgroup analysis revealed IQGAP3 expression correlated with radioresistance and was also an independent predictor of radiotherapy outcome.Conclusion: Our findings suggest that high IQGAP3 expression predicts poor prognosis and radioresistance in breast cancer. Therefore, IQGAP3 may be a reliable prognostic biomarker in breast cancer and could be used to identify patients who may benefit from radiotherapy.

scholarly journals IQGAP3 Overexpression Correlates with Poor Prognosis and Radiation Therapy Resistance in Breast Cancer

2018 ◽  
Author(s):  
Xin Hua ◽  
Zhi-Qing Long ◽  
Wen-Wen Zhang ◽  
Chao Lin ◽  
Xiao-Qing Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Protein Expression ◽  
Cancer Patients ◽  
Subgroup Analysis ◽  
Poor Prognosis ◽  
Therapy Resistance ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Tumor Tissues

AbstractBackground: IQ motif-containing GTPase activating protein 3 (IQGAP3), the latest found protein of IQGAP family, may act as a crucial factor in the process of cancer development and progression; however, its clinical value in breast cancer remains unestablished so far. Our team explored the correlation between IQGAP3 expression profile and the clinicopathological features in breast cancer. Methods: IQGAP3 levels in breast cancer cell lines and tumor tissues were detected by real-time PCR and western blotting and compared to the normal control groups. Protein expression of IQGAP3 was evaluated immunohistochemically in specimens (archived paraffin embedded) of 257 breast cancer patients. We also analyze the association between IQGAP3 expression and the clinical characters and prognosis. The relationship between IQGAP3 expression and sensitivity to radiation therapy was determined by subgroup analysis. Results: There was significant upregulation of IQGAP3 in breast cancer cell lines and human tumor tissues at both the mRNA and protein level compared to the normal ones. In addition, 110/257 (42.8%) of archived paraffin embedded breast cancer specimens had high protein expression of IQGAP3. High expression of IQGAP3 was significantly related to clinical stage (P=0.001), T category (P=0.002), N category (P=0.001), locoregional recurrence(P=0.002), distant metastasis (P=0.001), and vital status (P=0.001). Univariate and multivariate statistical analysis showed that IQGAP3 was an independent prognostic factor of the whole cohort breast cancer patients (P=0.003, P=0.001). Subgroup analysis revealed IQGAP3 expression correlates with radiation therapy resistance and was also an independent predictor for radiation therapy outcome. Conclusions: Our findings suggest that high IQGAP3 expression predicts poor prognosis and radiation therapy resistance in breast cancer. In addition, IQGAP3 may be a reliable novel biomarker to provide personalized prognostication and identify patients who can profit from more aggressive RT regimen for improving the survival of breast cancer patients.

scholarly journals Extracellular vesicles from young women’s breast cancer patients drive increased invasion of non-malignant cells via the Focal Adhesion Kinase pathway: a proteomic approach

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Kimberly R. Jordan ◽  
Jessica K. Hall ◽  
Troy Schedin ◽  
Michelle Borakove ◽  
Jenny J. Xian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Focal Adhesion ◽  
Invasive Breast Cancer ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Non Invasive ◽  
Healthy Donors

Abstract Background Extracellular vesicles (EVs) are small membrane particles that contribute to cancer progression and metastases by transporting biologically significant proteins and nucleic acids. They may also serve as biomarkers of various disease states or important therapeutic targets. Breast cancer EVs have the potential to change the behavior of other cells in their microenvironment. However, the proteomic content of EVs isolated from young women’s breast cancer patients and the mechanisms underlying the influence of EVs on tumor cell behavior have not yet been reported. Methods In our current translational studies, we compared the proteomic content of EVs isolated from invasive breast cancer cell lines and plasma samples from young women’s breast cancer (YWBC) patients and age-matched healthy donors using mass spectrometry. We analyzed the functionality of EVs in two dimensional tumor cell invasion assays and the gene expression changes in tumor cells after incubation with EVs. Results We found that treatment with EVs from both invasive breast cancer cell lines and plasma of YWBC patients altered the invasive properties of non-invasive breast cancer cells. Proteomics identified differences between EVs from YWBC patients and healthy donors that correlated with their altered function. Further, we identified gene expression changes in non-invasive breast cancer cells after treatment with EVs that implicate the Focal Adhesion Kinase (FAK) signaling pathway as a potential targetable pathway affected by breast cancer-derived EVs. Conclusions Our results suggest that the proteome of EVs from breast cancer patients reflects their functionality in tumor motility assays and may help elucidate the role of EVs in breast cancer progression.

scholarly journals Interaction between GRP78 and IGFBP-3 Affects Tumourigenesis and Prognosis in Breast Cancer Patients

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3821
Author(s):  
Hanna A. Zielinska ◽  
Carl S. Daly ◽  
Ahmad Alghamdi ◽  
Amit Bahl ◽  
Muhammed Sohail ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Survival Rates ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Kaplan Meier ◽  
Induced Apoptosis ◽  
Igfbp 3

Insulin-like growth factor binding protein 3 (IGFBP-3) plays a key role in breast cancer progression and was recently shown to bind to the chaperone protein glucose-regulated protein 78 (GRP78); however, the clinical significance of this association remains poorly investigated. Here we report a direct correlation between the expression of GRP78 and IGFBP-3 in breast cancer cell lines and tumour sections. Kaplan–Meier survival plots revealed that patients with low GRP78 expression that are positive for IGFBP-3 had poorer survival rates than those with low IGFBP-3 levels, and we observed a similar trend in the publicly available METABRIC gene expression database. With breast cancer cells, in vitro IGFBP-3 enhanced induced apoptosis, however when GRP78 expression was silenced the actions of IGFBP-3 were switched from increasing to inhibiting ceramide (C2)-induced cell death and promoted cell invasion. Using immunofluorescence and cell surface biotinylation, we showed that knock-down of GRP78 negated the entry of IGFBP-3 into the cells. Together, our clinical and experimental results suggest that loss of GRP78 reduces IGFBP-3 entry into cells switching its actions to promote tumorigenesis and predicts a poor prognosis in breast cancer patients.

scholarly journals AKR1B1 promotes basal-like breast cancer progression by a positive feedback loop that activates the EMT program

2017 ◽  
Vol 214 (4) ◽  
pp. 1065-1079 ◽  
Author(s):  
Xuebiao Wu ◽  
Xiaoli Li ◽  
Qiang Fu ◽  
Qianhua Cao ◽  
Xingyu Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Positive Feedback ◽  
Poor Prognosis ◽  
Feedback Loop ◽  
Epithelial Mesenchymal Transition ◽  
Breast Cancer Patients ◽  
Positive Feedback Loop ◽  
Mesenchymal Transition ◽  
Basal Like Breast Cancer

Basal-like breast cancer (BLBC) is associated with high-grade, distant metastasis and poor prognosis. Elucidating the determinants of aggressiveness in BLBC may facilitate the development of novel interventions for this challenging disease. In this study, we show that aldo-keto reductase 1 member B1 (AKR1B1) overexpression highly correlates with BLBC and predicts poor prognosis in breast cancer patients. Mechanistically, Twist2 transcriptionally induces AKR1B1 expression, leading to nuclear factor κB (NF-κB) activation. In turn, NF-κB up-regulates Twist2 expression, thereby fulfilling a positive feedback loop that activates the epithelial–mesenchymal transition program and enhances cancer stem cell (CSC)–like properties in BLBC. AKR1B1 expression promotes, whereas AKR1B1 knockdown inhibits, tumorigenicity and metastasis. Importantly, epalrestat, an AKR1B1 inhibitor that has been approved for the treatment of diabetic complications, significantly suppresses CSC properties, tumorigenicity, and metastasis of BLBC cells. Together, our study identifies AKR1B1 as a key modulator of tumor aggressiveness and suggests that pharmacologic inhibition of AKR1B1 has the potential to become a valuable therapeutic strategy for BLBC.

IQ Motif-Containing GTPase-Activating Protein 3 Overexpression Correlates with Poor Prognosis and Radiation Therapy Resistance in Breast Cancer

2019 ◽  
Vol 11 (5) ◽  
pp. 653-663
Author(s):  
Xin Hua ◽  
Qihang Yan ◽  
Zhiqing Long ◽  
Xin Huang ◽  
Jiapeng Deng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Cancer Patients ◽  
Subgroup Analysis ◽  
Therapy Resistance ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Gtpase Activating Protein ◽  
Iq Motif ◽  
Tumor Tissues

IQ motif-containing GTPase-activating protein 3 (IQGAP3), the latest found IQGAP family protein, may act as a crucial factor in the process of cancer development and progression; however, its clinical value in breast cancer remains unestablished so far. Our team explored the correlation between the IQGAP3 expression profile and clinicopathological features in breast cancer. IQGAP3 levels in breast cancer cell lines and tumor tissues were detected through real-time PCR and western blotting. We evaluated IQGAP3 expression in archived paraffin-embedded tissue specimens of 257 breast cancer patients, and determined the relationship between IQGAP3 expression and sensitivity to radiation therapy (RT), using subgroup analysis. We also analyzed the association between IQGAP3 expression and the clinical characters and prognosis of breast cancer. There was a significant upregulation of IQGAP3 in breast cancer cell lines and human tumor tissues at both mRNA and protein levels. In addition, 42.8% of the breast cancer specimens had high expression of IQGAP3, which was significantly related to clinical stage (P = 0.001), T category (P = 0.002), N category (P = 0.001), locoregional recurrence (P = 0.002), distant metastasis (P = 0.001), and vital status (P = 0.001). Univariate and multivariate statistical analyses showed that IQGAP3 is an independent prognostic factor for all the breast cancer patients (P = 0.003, P = 0.001). Subgroup analysis revealed that IQGAP3 expression is correlated with radiation therapy resistance and is an independent predictor for radiation therapy outcome. Our findings suggest that IQGAP3 may be a reliable novel biomarker to provide personalized prognosis and identify patients who can profit from a more aggressive RT regimen for improving breast cancer patient survival.

SIRT1 against breast cancer through downregulating Bcl-2 protein.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 34-34
Author(s):  
Dar-Ren Chen
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cell Lines ◽  
Cellular Proliferation ◽  
Tumor Promoter ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Class Iii ◽  
Tumor Tissues ◽  
Mcf 7

34 Background: SIRT1, a member of the class III histone deacetylase (HDAC) family, is the mammalian orthologue of yeast Sir2. It has been reported to play a key role in a variety of physiological processes such as genomic stability, metabolism, neurogenesis and cell survival due to its ability to deacetylate both histone and numerous non-histone substrates. The deacetylase function of SIRT1 has been suggested as playing a role in prolonging the life of mammals. However, the suggested functions of SIRT1 as a potential tumor promoter have been challenged by observations of their respective down- and up-regulation in various cancers. The aim of the present study was to simultaneously evaluate the expression levels of SIRT1 and Ki67, the index of cellular proliferation, in normal and tumor tissues of the breast from 27 breast cancer patients and to determine the role of SIRT1 in breast tumorigenesis. Methods: A total of 27 breast cancer patients were included. Tumor tissues and matched normal breast tissues were immediately frozen after collection between 2007 and 2008. Immunohistochemistry and reverse transcription-polymerase chain reaction were applied for analyses of patients’ specimens. Cell proliferation assay, cell cycle analysis and Western blotting were used to investigate the effects of sirtinol on the human breast cancer lines MCF-7 and MDA-MB-231 cells. Results: Immunohistochemistry showed that there is a high correlation between SIRT1 and Ki67 expression. In addition, our results showed that inhibition of SIRT1 induces anti-cell growth in both MCF-7 (ER-positive, non-invasive) and MDA-MB-231 (ER-negative, invasive) breast cancer cell lines, especially in MDA-MB-231 cells. The levels of pro-survival protein Bcl-2 were dramatically decreased in both breast cell lines following sirtinol treatment. Conclusions: Our present study revealed that inhibition of SIRT1 activity may be a promising chemotherapeutic strategy against breast cancer.

scholarly journals The high expression of NUDT5 indicates poor prognosis of breast cancer by modulating AKT / Cyclin D signaling

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0245876
Author(s):  
He Zhang ◽  
Li-Qun Zhang ◽  
Cheng-Cheng Yang ◽  
Jin Li ◽  
Xin-Yuan Tian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Tumor ◽  
Poor Prognosis ◽  
High Expression ◽  
Breast Cancer Cell Lines ◽  
Cyclin D ◽  
Tumor Tissues

NUDIX hydrolase type 5 (NUDT5) is a kind of ADP-ribose pyrophosphatase and nucleotide metabolizing enzyme in cell metabolism. Previous studies have shown NUDT5 expression affected chromosome remodeling, involved in cell adhesion, cancer stem cell maintenance and epithelial to mesenchyme transition in breast cancer cells. Nevertheless, the role of NUDT5 in breast cancer progression and prognosis has not yet been systematically studied. This study explored the association of NUDT5 with the tumor development and poor prognosis in patients with breast cancer. Our results show that the levels of NUDT5 were upregulated in breast cancer cell lines and breast tumor tissues, and the expression of NUDT5 in breast tumor tissues increased significantly when compared with adjacent non-tumorous tissues by immunohistochemical staining of tissue microarrays. Breast cancer patients with high NUDT5 expression had a worse prognosis than those with low expression of NUDT5. In addition, the knockdown of NUDT5 suppressed breast cancer cell lines proliferation, migration and invasion, and dramatically inhibited the AKT phosphorylation at Thr308 and expression of Cyclin D1. The opposite effects were observed in vitro following NUDT5 rescue. Our findings indicated that the high expression of NUDT5 is probably involved in the poor prognosis of breast cancer via the activation of the AKT / Cyclin D pathways, which could be a prognostic factor and potential target in the diagnosis and treatment of breast cancer.

Overexpression of microRNA-21 in the Serum of Breast Cancer Patients

MicroRNA ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 58-63
Author(s):  
Batool Savari ◽  
Sohrab Boozarpour ◽  
Maryam Tahmasebi-Birgani ◽  
Hossein Sabouri ◽  
Seyed Mohammad Hosseini
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Tumor Resection ◽  
Tumor Grade ◽  
Healthy Controls ◽  
Breast Cancer Patients ◽  
Serum Samples ◽  
Post Surgery ◽  
Polymerase Chain

Background: Breast cancer is the most common cancer diagnosed in women worldwide. So it seems that there's a good chance of recovery if it's detected in its early stages even before the appearances of symptoms. Recent studies have shown that miRNAs play an important role during cancer progression. These transcripts can be tracked in liquid samples to reveal if cancer exists, for earlier treatment. MicroRNA-21 (miR-21) has been shown to be a key regulator of carcinogenesis, and breast tumor is no exception. Objective: The present study was aimed to track the miR-21 expression level in serum of the breast cancer patients in comparison with that of normal counterparts. Methods: Comparative real-time polymerase chain reaction was applied to determine the levels of expression of miR-21 in the serum samples of 57 participants from which, 42 were the patients with breast cancer including pre-surgery patients (n = 30) and post-surgery patients (n = 12), and the others were the healthy controls (n = 15). Results: MiR-21 was significantly over expressed in the serum of breast cancer patients as compared with healthy controls (P = 0.002). A significant decrease was also observed following tumor resection (P < 0.0001). Moreover, it was found that miR-21 overexpression level was significantly associated with tumor grade (P = 0.004). Conclusion: These findings suggest that miR-21 has the potential to be used as a novel breast cancer biomarker for early detection and prognosis, although further experiments are needed.

scholarly journals Down-Regulation of the Proteoglycan Decorin Fills in the Tumor-Promoting Phenotype of Ionizing Radiation-Induced Senescent Human Breast Stromal Fibroblasts

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1987
Author(s):  
Eleni Mavrogonatou ◽  
Adamantia Papadopoulou ◽  
Asimina Fotopoulou ◽  
Stathis Tsimelis ◽  
Heba Bassiony ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ionizing Radiation ◽  
Cancer Progression ◽  
Breast Cancer Cell Lines ◽  
Phenotypic Trait ◽  
Mrna Levels ◽  
Human Breast ◽  
Down Regulation ◽  
Stromal Fibroblasts ◽  
Poor Prognostic Factor

Down-regulation of the small leucine-rich proteoglycan decorin in the stroma is considered a poor prognostic factor for breast cancer progression. Ionizing radiation, an established treatment for breast cancer, provokes the premature senescence of the adjacent to the tumor stromal fibroblasts. Here, we showed that senescent human breast stromal fibroblasts are characterized by the down-regulation of decorin at the mRNA and protein level, as well as by its decreased deposition in the pericellular extracellular matrix in vitro. Senescence-associated decorin down-regulation is a long-lasting process rather than an immediate response to γ-irradiation. Growth factors were demonstrated to participate in an autocrine manner in decorin down-regulation, with bFGF and VEGF being the critical mediators of the phenomenon. Autophagy inhibition by chloroquine reduced decorin mRNA levels, while autophagy activation using the mTOR inhibitor rapamycin enhanced decorin transcription. Interestingly, the secretome from a series of both untreated and irradiated human breast cancer cell lines with different molecular profiles inhibited decorin expression in young and senescent stromal fibroblasts, which was annulled by SU5402, a bFGF and VEGF inhibitor. The novel phenotypic trait of senescent human breast stromal fibroblasts revealed here is added to their already described cancer-promoting role via the formation of a tumor-permissive environment.

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