scholarly journals The p140Cap adaptor protein as a molecular hub to block cancer aggressiveness

2020 ◽  
Author(s):  
Vincenzo Salemme ◽  
Costanza Angelini ◽  
Jennifer Chapelle ◽  
Giorgia Centonze ◽  
Dora Natalini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Adaptor Protein ◽  
Lower Probability ◽  
Mrna Levels ◽  
Loss Of Function ◽  
Primary Tumors ◽  
Cancer Aggressiveness ◽  
The Impact

Abstract The p140Cap adaptor protein is a scaffold molecule encoded by the SRCIN1 gene, which is physiologically expressed in several epithelial tissues and in the neurons. However, p140Cap is also strongly expressed in a significant subset of cancers including breast cancer and neuroblastoma. Notably, cancer patients with high p140Cap expression in their primary tumors have a lower probability of developing a distant event and ERBB2-positive breast cancer sufferers show better survival. In neuroblastoma patients, SRCIN1 mRNA levels represent an independent risk factor, which is inversely correlated to disease aggressiveness. Consistent with clinical data, SRCIN1 gain or loss of function mouse models demonstrated that p140Cap may affect tumor growth and metastasis formation by controlling the signaling pathways involved in tumorigenesis and metastatic features. This study reviews data showing the relevance of SRCIN1/p140Cap in cancer patients, the impact of SRCIN1 status on p140Cap expression, the specific mechanisms through which p140Cap can limit cancer progression, the molecular functions regulated by p140Cap, along with the p140Cap interactome, to unveil its key role for patient stratification in clinics.

scholarly journals GREM1 is associated with metastasis and predicts poor prognosis in ER-negative breast cancer patients

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Ulrike Neckmann ◽  
Camilla Wolowczyk ◽  
Martina Hall ◽  
Eivind Almaas ◽  
Jiang Ren ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cell Lines ◽  
Poor Prognosis ◽  
Expression Patterns ◽  
Stem Cell Markers ◽  
Mrna Levels ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Bmp Antagonists

Abstract Background In breast cancer, activation of bone morphogenetic protein (BMP) signaling and elevated levels of BMP-antagonists have been linked to tumor progression and metastasis. However, the simultaneous upregulation of BMPs and their antagonist, and the fact that both promote tumor aggressiveness seems contradictory and is not fully understood. Methods We analyzed the transcriptomes of the metastatic 66cl4 and the non-metastatic 67NR cell lines of the 4T1 mouse mammary tumor model to search for factors that promote metastasis. CRISPR/Cas9 gene editing was used for mechanistic studies in the same cell lines. Furthermore, we analyzed gene expression patterns in human breast cancer biopsies obtained from public datasets to evaluate co-expression and possible relations to clinical outcome. Results We found that mRNA levels of the BMP-antagonist Grem1, encoding gremlin1, and the ligand Bmp4 were both significantly upregulated in cells and primary tumors of 66cl4 compared to 67NR. Depletion of gremlin1 in 66cl4 could impair metastasis to the lungs in this model. Furthermore, we found that expression of Grem1 correlated with upregulation of several stem cell markers in 66cl4 cells compared to 67NR cells. Both in the mouse model and in patients, expression of GREM1 associated with extracellular matrix organization, and formation, biosynthesis and modification of collagen. Importantly, high expression of GREM1 predicted poor prognosis in estrogen receptor negative breast cancer patients. Analyses of large patient cohorts revealed that amplification of genes encoding BMP-antagonists and elevation of the corresponding transcripts is evident in biopsies from more than half of the patients and much more frequent for the secreted BMP-antagonists than the intracellular inhibitors of SMAD signaling. Conclusion In conclusion, our results show that GREM1 is associated with metastasis and predicts poor prognosis in ER-negative breast cancer patients. Gremlin1 could represent a novel target for therapy.

scholarly journals Paradoxical Association of Postoperative Plasma Sphingosine-1-Phosphate with Breast Cancer Aggressiveness and Chemotherapy

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Rajesh Ramanathan ◽  
Ali Raza ◽  
Jamie Sturgill ◽  
Debra Lyon ◽  
Jessica Young ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Regulatory Function ◽  
Lipid Mediator ◽  
Breast Cancer Patients ◽  
Cancer Aggressiveness ◽  
Sphingosine 1 Phosphate ◽  
Healthy Control

Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator that has been shown to serve an important regulatory function in breast cancer progression. This study analyzes plasma S1P levels in breast cancer patients undergoing adjuvant therapy as compared to healthy control volunteers. 452 plasma S1P samples among 158 breast cancer patients, along with 20 healthy control volunteers, were analyzed. Mean S1P levels did not significantly differ between cancer patients and controls. Smoking was associated with higher S1P levels in cancer patients. Baseline S1P levels had weak inverse correlation with levels of the inflammatory mediator interleukin- (IL-) 17 and CCL-2 and positive correlation with tumor necrosis factor alpha (TNF-α). Midpoint S1P levels during adjuvant therapy were lower than baseline, with near return to baseline after completion, indicating a relationship between chemotherapy and circulating S1P. While stage of disease did not correlate with plasma S1P levels, they were lower among patients with Her2-enriched and triple-negative breast cancer as compared to luminal-type breast cancer. Plasma S1P levels are paradoxically suppressed in aggressive breast cancer and during adjuvant chemotherapy, which raises the possibility that postoperative plasma S1P levels do not reflect S1P secretion from resected breast cancer.

scholarly journals High level of EGF-R expression in carcinomatous skin invasion: Does it reflect the tissue characteristics of the breast carcinoma aggressiveness?

2002 ◽  
Vol 10 (3) ◽  
pp. 111-114
Author(s):  
Zora Neskovic-Konstantinovic ◽  
Dragica Nikolic-Vukosavljevic ◽  
Ksenija Kanjer ◽  
Danica Jovanovic ◽  
Mirjana Brankovic-Magic
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Inflammatory Breast Cancer ◽  
Normal Skin ◽  
Locally Advanced ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Number Of Patients ◽  
Cancer Aggressiveness

Background: The normal function and distribution of EGF-R and its role in breast cancer aggressiveness, prognosis and prediction, have become extremely important in the light of the recently developed methods of EGF-R targeting. In the aim to investigate the relationship between EGF-R and the aggressive tumor behavior, the EGF-R content was analyzed as related to the presence of inflammatory breast skin involvement. Methods: EGF-R, ER and PR content was determined at diagnosis, using the biochemical methods, in the group of 103 unselected breast cancer patients, either in primary tumors (TU), lymph nodes (LN) or skin tissue samples (65, 27 and 11 cases respectively). In 10 patients with inflammatory breast cancers, TU/LN tissue was sampled from 3, and skin from 7 patients. Results: ER and PR content was significantly higher in tumor and LN tissue, compared to the invaded skin the EGF-R content was, on the contrary, significantly higher in skin than in TU or LN tissue. However, no difference was found between TU and LN in all three receptors' content. When the receptor content was analyzed in 10 patients with inflammatory breast cancer, higher levels of both ER and PR were found in tumor biopsies than in skin biopsies, while for the EGF-R the result was opposite. Significantly lower ER content and a trend towards higher EGF-R content was found in the inflammatory breast cancers in comparison to the non-inflammatory ones. Conclusion: Although we examined a small number of patients, our results suggest that the EGF-R could be a marker of breast cancer aggressiveness. However, the influence of the normal skin cells contaminating the biopsied tumor tissue cannot be ruled out. The predictive role of EGF-R deserves to be further investigated especially in locally advanced inflammatory breast cancer patients.

scholarly journals An epithelial-mesenchymal-amoeboid transition gene signature reveals subtypes of breast cancer progression and metastasis

2017 ◽  
Author(s):  
Amin Emad ◽  
Tania Ray ◽  
Tor W. Jensen ◽  
Meera Parat ◽  
Rachael Natrajan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Gene Signature ◽  
Breast Cancer Progression ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Node Negative ◽  
Node Negative Breast Cancer

AbstractCancer cells within a tumor are known to display varying degrees of metastatic propensity but the molecular basis underlying such heterogeneity remains unclear. We analyzed genome-wide gene expression data obtained from primary tumors of lymph node-negative breast cancer patients using a novel metastasis biology-based Epithelial-Mesenchymal-Amoeboid Transition (EMAT) gene signature, and identified subtypes associated with distinct prognostic profiles. EMAT subtype status improved prognosis accuracy of clinical parameters and statistically outperformed traditional breast cancer intrinsic subtypes even after adjusting for treatment variables. Additionally, analysis of 3D spheroids from an in vitro isogenic model of breast cancer progression reveals that EMAT subtypes display progression from premalignant to malignant and pre-invasive to invasive cancer. EMAT classification is a biologically informed method to assess metastasis risk in early stage, lymph node-negative breast cancer patients.

scholarly journals Tumor apelin and obesity are associated with reduced neoadjuvant chemotherapy response in a cohort of breast cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Florian Gourgue ◽  
Françoise Derouane ◽  
Cedric van Marcke ◽  
Elodie Villar ◽  
Helene Dano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Disease Free Survival ◽  
Chemotherapy Response ◽  
Breast Cancer Patients ◽  
Response To Chemotherapy ◽  
Two Parameters ◽  
The Impact

AbstractObesity is a known factor increasing the risk of developing breast cancer and reducing disease free survival. In addition to these well-documented effects, recent studies have shown that obesity is also affecting response to chemotherapy. Among the multiple dysregulations associated with obesity, increased level of the apelin adipokine has been recently shown to be directly involved in the association between obesity and increased breast cancer progression. In this study, we analyzed in a retrospective cohort of 62 breast cancer patients the impact of obesity and tumoral apelin expression on response to neoadjuvant chemotherapy. In the multivariate logistic regression, obesity and high tumoral apelin expression were associated with a reduced response to NAC in our cohort. However, obesity and high tumoral apelin expression were not correlated, suggesting that those two parameters could be independently associated with reduced NAC response. These findings should be confirmed in independent cohorts.

Psychosocial Interventions for Depressed Breast Cancer Patients

2014 ◽  
Author(s):  
Derek R. Hopko ◽  
Crystal C. McIndoo ◽  
Michael Gawrysiak ◽  
Stevie Grassetti
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Behavioral Assessment ◽  
Psychosocial Interventions ◽  
Medical Illness ◽  
Breast Cancer Patients ◽  
Life Functioning ◽  
Assessment Strategies ◽  
The Impact

Clinical depression affects many people and is associated with several risk factors that include being diagnosed with a serious medical illness such as breast cancer. Objectives of this chapter were to elucidate the prevalence of depression in breast cancer patients, the impact of depression as it pertains to life functioning and quality of life, highlight the bidirectional relationship of breast cancer and depression, outline assessment strategies and measurement issues relevant to assessing depression, and review the treatment outcome literature addressing the efficacy of psychosocial interventions for depressed breast cancer patients. Depression is highly prevalent among breast cancer patients, significantly impacts life functioning, may be associated with cancer progression and mortality, and is bidirectionally related to breast cancer through several pathways. Many behavioral assessment strategies may be useful for recognizing depression in breast cancer patients, and, although methodological weaknesses are evident, several psychosocial interventions show substantial promise as effective treatments for depressed breast cancer patients.

Diagnostic Value of VDR in Bone Metastasis and Prognosis of Patients with Breast Cancer and Expression Correlation between VDR and Hr

2021 ◽  
Author(s):  
Pan Ding ◽  
XiaoMing Du ◽  
LiHui Wan ◽  
Xueke Zhao ◽  
DeRui Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Diagnostic Value ◽  
Normal Breast ◽  
Mrna Levels ◽  
Breast Cancer Patients ◽  
Protein Levels ◽  
Low Expression

Background: Breast cancer is more likely to metastasize to the bone. Previous researches have revealed that vitamin D receptor (VDR) contributes to breast cancer progression and bone metastasis in mouse and human breast cells, and Hairless (Hr) protein interacts with VDR in the mammalian hair cycle. This study aimed to explore the expression of VDR/Hr in breast cancer, and the correlation between VDR/Hr and prognosis, bone metastasis, and metastasis-related prognosis. Methods: The expression of VDR and Hr was performed on 119 breast cancer tissues and corresponding normal breast tissue from each of the breast cancer samples by Immunohistochemistry (IHC) staining, and the databases were supplemented as well. Results: The expression of VDR protein was significantly decreased in breast cancer patients (p < 0.05), inversely, the UALCAN (p = 0.000) and GEPIA (p > 0.05) databases showed VDR mRNA expression tended to be higher in tumor tissues. Hr protein was expressed at low level within breast cancer specimens (p < 0.05), which was in agreement with the level of Hr mRNA in the UALCAN (p = 0.005) and GEPIA (p > 0.05). The protein levels of VDR and Hr were positively correlated (p > 0.05), while the mRNA levels suggested a closely relationship in the GEPIA (p < 0.05). Low expression of Hr protein displayed a tendency for longer overall survival (OS) and recurrence-free survival (RFS), and its mRNA data also revealed the same trend in the KM dataset (both p > 0.05). Whereas, VDR protein and mRNA low expression had markedly shorter OS and RFS (both p < 0.05). The down-regulation of VDR protein was significantly associated with advanced stage (p < 0.05). Low VDR protein was an independent risk factor for poor prognosis (p < 0.05) and was negatively correlated with bone metastasis (p < 0.05). VDR protein and mRNA levels were both down-regulated in breast cancer with bone metastasis (both p < 0.05). The area under ROC curve (AUC) for VDR protein expression to identify patients with bone metastasis was 0.661 (p < 0.05) and the AUC for VDR level to predict 1-year 3-year, 5-year OS was 0.621, 0.664, and 0.805 in patients with bone metastasis, respectively (p < 0.05). VDR low expression accelerated bone metastasis and metastasis-related poor survival (both p < 0.05). Conclusion: VDR expression is a notably prognostic factor in primary breast cancer patients for predicting bone metastases and unfavorable clinical outcome.

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 MCM3 upregulation confers endocrine resistance in breast cancer and is a predictive marker of diminished tamoxifen benefit

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Sanne Løkkegaard ◽  
Daniel Elias ◽  
Carla L. Alves ◽  
Martin V. Bennetzen ◽  
Anne-Vibeke Lænkholm ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Endocrine Resistance ◽  
Predictive Marker ◽  
Endocrine Treatment ◽  
Breast Cancer Patients ◽  
Minichromosome Maintenance ◽  
Primary Tumors

AbstractResistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer is a major clinical problem with poorly understood mechanisms. There is an unmet need for prognostic and predictive biomarkers to allow appropriate therapeutic targeting. We evaluated the mechanism by which minichromosome maintenance protein 3 (MCM3) influences endocrine resistance and its predictive/prognostic potential in ER+ breast cancer. We discovered that ER+ breast cancer cells survive tamoxifen and letrozole treatments through upregulation of minichromosome maintenance proteins (MCMs), including MCM3, which are key molecules in the cell cycle and DNA replication. Lowering MCM3 expression in endocrine-resistant cells restored drug sensitivity and altered phosphorylation of cell cycle regulators, including p53(Ser315,33), CHK1(Ser317), and cdc25b(Ser323), suggesting that the interaction of MCM3 with cell cycle proteins is an important mechanism of overcoming replicative stress and anti-proliferative effects of endocrine treatments. Interestingly, the MCM3 levels did not affect the efficacy of growth inhibitory by CDK4/6 inhibitors. Evaluation of MCM3 levels in primary tumors from four independent cohorts of breast cancer patients receiving adjuvant tamoxifen mono-therapy or no adjuvant treatment, including the Stockholm tamoxifen (STO-3) trial, showed MCM3 to be an independent prognostic marker adding information beyond Ki67. In addition, MCM3 was shown to be a predictive marker of response to endocrine treatment. Our study reveals a coordinated signaling network centered around MCM3 that limits response to endocrine therapy in ER+ breast cancer and identifies MCM3 as a clinically useful prognostic and predictive biomarker that allows personalized treatment of ER+ breast cancer patients.

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