scholarly journals Ceramide Metabolism Balance, a Multifaceted Factor in Critical Steps of Breast Cancer Development

2018 ◽  
Vol 19 (9) ◽  
pp. 2527 ◽  
Author(s):  
Victor García-González ◽  
José Díaz-Villanueva ◽  
Octavio Galindo-Hernández ◽  
Israel Martínez-Navarro ◽  
Gustavo Hurtado-Ureta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Chemotherapy Resistance ◽  
Cell Communication ◽  
Low Grade ◽  
Cancer Disease ◽  
Cellular Processes ◽  
Neoplastic Processes ◽  
Key Factor ◽  
Inflammatory State

Ceramides are key lipids in energetic-metabolic pathways and signaling cascades, modulating critical physiological functions in cells. While synthesis of ceramides is performed in endoplasmic reticulum (ER), which is altered under overnutrition conditions, proteins associated with ceramide metabolism are located on membrane arrangement of mitochondria and ER (MAMs). However, ceramide accumulation in meta-inflammation, condition that associates obesity with a chronic low-grade inflammatory state, favors the deregulation of pathways such as insulin signaling, and induces structural rearrangements on mitochondrial membrane, modifying its permeability and altering the flux of ions and other molecules. Considering the wide biological processes in which sphingolipids are implicated, they have been associated with diseases that present abnormalities in their energetic metabolism, such as breast cancer. In this sense, sphingolipids could modulate various cell features, such as growth, proliferation, survival, senescence, and apoptosis in cancer progression; moreover, ceramide metabolism is associated to chemotherapy resistance, and regulation of metastasis. Cell–cell communication mediated by exosomes and lipoproteins has become relevant in the transport of several sphingolipids. Therefore, in this work we performed a comprehensive analysis of the state of the art about the multifaceted roles of ceramides, specifically the deregulation of ceramide metabolism pathways, being a key factor that could modulate neoplastic processes development. Under specific conditions, sphingolipids perform important functions in several cellular processes, and depending on the preponderant species and cellular and/or tissue status can inhibit or promote the development of metabolic and potentially breast cancer disease.

scholarly journals Bone morphogenetic proteins, breast cancer, and bone metastases: striking the right balance

2017 ◽  
Vol 24 (10) ◽  
pp. R349-R366 ◽  
Author(s):  
Catherine Zabkiewicz ◽  
Jeyna Resaul ◽  
Rachel Hargest ◽  
Wen Guo Jiang ◽  
Lin Ye
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Bone Morphogenetic Proteins ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Breast Tumour ◽  
Cellular Functions ◽  
Foetal Development ◽  
Key Factor ◽  
The Right

Bone morphogenetic proteins (BMPs) belong to the TGF-β super family, and are essential for the regulation of foetal development, tissue differentiation and homeostasis and a multitude of cellular functions. Naturally, this has led to the exploration of aberrance in this highly regulated system as a key factor in tumourigenesis. Originally identified for their role in osteogenesis and bone turnover, attention has been turned to the potential role of BMPs in tumour metastases to, and progression within, the bone niche. This is particularly pertinent to breast cancer, which commonly metastasises to bone, and in which studies have revealed aberrations of both BMP expression and signalling, which correlate clinically with breast cancer progression. Ultimately a BMP profile could provide new prognostic disease markers. As the evidence suggests a role for BMPs in regulating breast tumour cellular function, in particular interactions with tumour stroma and the bone metastatic microenvironment, there may be novel therapeutic potential in targeting BMP signalling in breast cancer. This review provides an update on the current knowledge of BMP abnormalities and their implication in the development and progression of breast cancer, particularly in the disease-specific bone metastasis.

scholarly journals PCDHGB7 Increases Chemosensitivity to Carboplatin by Inhibiting HSPA9 via Inducing Apoptosis in Breast Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Siqi Hou ◽  
Ming Shan ◽  
Chunyang Gao ◽  
Xinxin Feng ◽  
Yongheng Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Caspase 3 ◽  
Triple Negative ◽  
Chemotherapy Resistance ◽  
Underlying Mechanism ◽  
High Recurrence Rate ◽  
Tnbc Cell ◽  
Resistance To Chemotherapy

Breast cancer is one of the most serious cancers worldwide, and chemotherapy resistance frequently drives cancer progression. Triple-negative breast cancer (TNBC) has a high recurrence rate and poor prognosis given its resistance to chemotherapy. In our previous study, we found a remarkable abnormal methylation modification of the PCDHGB7 gene in breast cancer. However, the roles of PCDHGB7 in the progression and treatment of breast cancer are unclear. In this study, we examined the effects of PCDHGB7 on the sensitivity of TNBC cells to carboplatin and investigated the underlying mechanism. By knocking down and overexpressing PCDHGB7 in HS578T and BT549 cells, we confirmed that PCDHGB7 increases TNBC cell chemosensitivity to carboplatin. Mechanistically, we found that PCDHGB7 negatively regulates the expression of HSPA9, uplifting its inhibition on P53 translocation and caspase-3 activation. Thus, we demonstrated that PCDHGB7 increases chemosensitivity of TNBC cells to carboplatin by inhibiting HSPA9 via inducing apoptosis. PCDHGB7 and HSPA9 represent potential therapeutic targets for chemosensitivity in breast cancer.

scholarly journals Overcoming Therapy Resistance and Relapse in TNBC: Emerging Technologies to Target Breast Cancer-Associated Fibroblasts

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1921
Author(s):  
Farhana Mollah ◽  
Pegah Varamini
Keyword(s):  
Breast Cancer ◽  
Small Molecules ◽  
Cancer Progression ◽  
Triple Negative ◽  
Chemotherapy Resistance ◽  
Therapy Resistance ◽  
Cancer Associated Fibroblasts ◽  
Aggressive Form ◽  
Promising Target ◽  
Wide Range

Breast cancer is the most diagnosed cancer and is the leading cause of cancer mortality in women. Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer. Often, TNBC is not effectively treated due to the lack of specificity of conventional therapies and results in relapse and metastasis. Breast cancer-associated fibroblasts (BCAFs) are the predominant cells that reside in the tumor microenvironment (TME) and regulate tumorigenesis, progression and metastasis, and therapy resistance. BCAFs secrete a wide range of factors, including growth factors, chemokines, and cytokines, some of which have been proved to lead to a poor prognosis and clinical outcomes. This TME component has been emerging as a promising target due to its crucial role in cancer progression and chemotherapy resistance. A number of therapeutic candidates are designed to effectively target BCAFs with a focus on their tumor-promoting properties and tumor immune response. This review explores various agents targeting BCAFs in TNBC, including small molecules, nucleic acid-based agents, antibodies, proteins, and finally, nanoparticles.

scholarly journals Pannexin1 Is Associated with Enhanced Epithelial-To-Mesenchymal Transition in Human Patient Breast Cancer Tissues and in Breast Cancer Cell Lines

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1967 ◽  
Author(s):  
Nour Jalaleddine ◽  
Layal El-Hajjar ◽  
Hassan Dakik ◽  
Abdullah Shaito ◽  
Jessica Saliba ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Cell Communication ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Breast Cancer Cell Lines ◽  
Mesenchymal Transition ◽  
Genetic Ablation ◽  
Functional Features

Loss of connexin-mediated cell-cell communication is a hallmark of breast cancer progression. Pannexin1 (PANX1), a glycoprotein that shares structural and functional features with connexins and engages in cell communication with its environment, is highly expressed in breast cancer metastatic foci; however, PANX1 contribution to metastatic progression is still obscure. Here we report elevated expression of PANX1 in different breast cancer (BRCA) subtypes using RNA-seq data from The Cancer Genome Atlas (TCGA). The elevated PANX1 expression correlated with poorer outcomes in TCGA BRCA patients. In addition, gene set enrichment analysis (GSEA) revealed that epithelial-to-mesenchymal transition (EMT) pathway genes correlated positively with PANX1 expression. Pharmacological inhibition of PANX1, in MDA-MB-231 and MCF-7 breast cancer cells, or genetic ablation of PANX1, in MDA-MB-231 cells, reverted the EMT phenotype, as evidenced by decreased expression of EMT markers. In addition, PANX1 inhibition or genetic ablation decreased the invasiveness of MDA-MB-231 cells. Our results suggest PANX1 overexpression in breast cancer is associated with a shift towards an EMT phenotype, in silico and in vitro, attributing to it a tumor-promoting effect, with poorer clinical outcomes in breast cancer patients. This association offers a novel target for breast cancer therapy.

scholarly journals mTORC1 deregulation and increased invasiveness cohere with dispersed endolysosomes in high-grade bladder cancer

2020 ◽  
Author(s):  
Pallavi Mathur ◽  
Camilla De Barros Santos ◽  
Hugo Lachuer ◽  
Bruno Latgé ◽  
François Radvanyi ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Culture Conditions ◽  
Low Grade ◽  
High Grade ◽  
Ph Homeostasis ◽  
Cancer Disease ◽  
Mtorc1 Signaling

AbstractLate endosomes/lysosomes (endolysosomes) emerge as a potential regulatory hub during cancer. Here, we investigate the intracellular landscape of this organelle in a collection of bladder cancer cell lines and normal human urothelium cells under standardized culture conditions. We find that high-grade bladder cancer cells are characterized by scattered endolysosomes that are accompanied by an altered cellular pH homeostasis and major changes of mTORC1 regulation. Mechanistically, we reveal that mTORC1 substrate specificity is altered, and mTORC1 responsiveness to endolysosome positioning is lost in high-grade cancer cells compared to low-grade cells, highlighting unexpected mechanisms of mTORC1 deregulation in the bladder cancer model. Because endolysosome positioning was critical for invasion from 3D spheroids, our results indicate that changes in their cellular positioning and ability to support signaling, strongly impact cancer cell behavior. Thus, monitoring detailed changes of endolysosomes at different steps of cancer disease reveals intricate spatial and temporal dimensions of tumorigenesis.Statement of significanceOur study reveals significant changes of endolysosomes in bladder cancer progression, highlighting endolysosome dysfunction as a fundamental driving progress in malignancies. The identified alterations in endolysosome positioning and associated mTORC1 signaling regulation could help to stratify emerging therapeutic strategies targeting the endolysosomal compartment.

Semi-quantitative gene expression profiling for therapy prediction in a breast cancer neoadjuvant therapy study applying docetaxel/epirubicin/cyclophosphamide

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21144-21144
Author(s):  
U. Vogt ◽  
D. Kemming ◽  
B. Brandt ◽  
U. Bosse ◽  
U. Bonk ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Expression Profiling ◽  
Pearson Correlation ◽  
Neoadjuvant Treatment ◽  
Chemotherapy Resistance ◽  
Tumour Response ◽  
High Specificity ◽  
Cancer Genes ◽  
Breast Cancer Patients

21144 Background: More than 28000 curated human genes can be analyzed semi-quantitatively using a chemiluminescent detection technology and 60mer oligonucleotides on a Human Genome Survey Microarray (HGSM, Applied Biosytems). Methods: HGSM expression profiling was performed on biopsy samplesfrom a setting of patients under neoadjuvant treatment. The protocol for a phase II study was elaborated for the treatment of breast cancer patients suffering from a primary tumor > 1,5 cm or inflammatory breast cancer with Docetaxel / Epirubicin/Cyclophosphamide (TEC) prior to surgical treatment. The study was approved by the local ethical committee and 80 patients will be included into the study after written informed consent. 40 patients have been already included in the ongoing study. In this prospective study a biopsy from the tumor is taken before chemotherapy. Therefore, success of treatment is detectable directly at the operated residual tumor. Our results demonstrate a low rate of false-positives (1.2%), a high specificity and quantification accuracy of HGSM system. Comparison of data from HGSM and RT-PCR obtained on mRNA from fresh frozen tissue resulted a Pearson-correlation of 0.92 to 0.63 for the breast cancer genes. Results: Tumour response (pCR, pPR) of more than 70 % can be achieved using neoadjuvant TEC- regimen. 25 % of pCR in this study is comparable with data of other published neoadjuvant trails. First expression profiling results are obtainable showing that a subset of 148 genes indicates patients with complete remission (pCR, no detectable tumor at end of chemotherapy), partial remission (pPR) and progressive disease (pPD). Remarkable, that the expression profile clearly separated pCR and pPD tumors whereas pPR tumors presented with a closer relationship to pPD tumors than to pCR tumors but displayed small specific subprofiles. A comparable separation of the groups could not achieved by established tumor markers, e.g. ER, PgR, HER2, uPA etc. which are measured simultaneously on the HGSM. Conclusions: HGSM expression profiling is promising to have the potential to figure out genes that are related to cancer progression and chemotherapy resistance, especially in PST. No significant financial relationships to disclose.

scholarly journals Altered Sirtuin 7 Expression is Associated with Early Stage Breast Cancer

2015 ◽  
Vol 9 ◽  
pp. BCBCR.S23156 ◽  
Author(s):  
Ahmad Aljada ◽  
Ayman M. Saleh ◽  
Moath Alkathiri ◽  
Heba Bani Shamsa ◽  
Ahmad Al-Bawab ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Cancer Progression ◽  
Early Stage ◽  
Cdna Array ◽  
Normal Breast ◽  
Mrna Levels ◽  
Breast Cancer Patients ◽  
Cancer Disease ◽  
Expression Status

Background To evaluate sirtuin-7 (SirT7) mRNA expression status in breast cancer patients with different metastatic stages and survey SirT7 mRNA expression status in eight different types of cancer. Methods The expression of SirT7 in the commercially available TissueScan qPCR Breast Cancer Disease cDNA arrays containing 16 normal, 23 Stage I, 36 IIA, 22 IIB, 8 IIIA, 23 IIIA, 6 IIIB, 13 IIIC, and 5 IV were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Similar analysis was performed in TissueScan qPCR Cancer Survey cDNA array, which includes breast, colon, kidney, liver, lung, ovarian, prostate, and thyroid specimens. Results The mRNA expression levels of SirT7 were significantly higher in breast cancer samples compared to normal breast specimens ( P < 0.001). Stratification of patients into groups according to metastatic stages indicated statistically significantly higher levels of SirT7 mRNA in CS-I, CS-II, and CS-III when compared to normal breast tissue ( P < 0.05). Notably, SirT7 mRNA levels were higher in CS-I, CS-IIA, CS-IIB, and CS-IIIA ( P < 0.05). Additionally, there were significantly lower SirT7 mRNA levels in thyroid carcinoma when compared to their corresponding normal tissue ( P < 0.05). Conclusions Our results indicate an increase in the mRNA expression level of SirT7 in breast cancer, particularly in CS-I, CS-IIA, CS-IIB, and CS-IIIA. The relationship of altered SirT7 with breast cancer progression and patient survival should be prospectively explored in future studies.

scholarly journals Extracellular Matrix Influencing HGF/c-MET Signaling Pathway: Impact on Cancer Progression

2018 ◽  
Vol 19 (11) ◽  
pp. 3300 ◽  
Author(s):  
Heydi Noriega-Guerra ◽  
Vanessa Freitas
Keyword(s):  
Extracellular Matrix ◽  
Tumor Cell ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Cell Communication ◽  
Dynamic Network ◽  
Cell Types ◽  
Bioactive Molecules ◽  
Matricellular Proteins ◽  
Cellular Processes

The extracellular matrix (ECM) is a crucial component of the tumor microenvironment involved in numerous cellular processes that contribute to cancer progression. It is acknowledged that tumor–stromal cell communication is driven by a complex and dynamic network of cytokines, growth factors and proteases. Thus, the ECM works as a reservoir for bioactive molecules that modulate tumor cell behavior. The hepatocyte growth factor (HGF) produced by tumor and stromal cells acts as a multifunctional cytokine and activates the c-MET receptor, which is expressed in different tumor cell types. The HGF/c-MET signaling pathway is associated with several cellular processes, such as proliferation, survival, motility, angiogenesis, invasion and metastasis. Moreover, c-MET activation can be promoted by several ECM components, including proteoglycans and glycoproteins that act as bridging molecules and/or signal co-receptors. In contrast, c-MET activation can be inhibited by proteoglycans, matricellular proteins and/or proteases that bind and sequester HGF away from the cell surface. Therefore, understanding the effects of ECM components on HGF and c-MET may provide opportunities for novel therapeutic strategies. Here, we give a short overview of how certain ECM components regulate the distribution and activation of HGF and c-MET.

scholarly journals Non-Genomic Actions of Estrogens on the DNA Repair Pathways Are Associated With Chemotherapy Resistance in Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Javier E. Jiménez-Salazar ◽  
Rebeca Damian-Ferrara ◽  
Marcela Arteaga ◽  
Nikola Batina ◽  
Pablo Damián-Matsumura
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Dna Repair ◽  
Cancer Progression ◽  
Scientific Evidence ◽  
Chemotherapy Resistance ◽  
Estrogen Signaling ◽  
Repair Mechanisms ◽  
Long Time ◽  
Repair Pathways

Estrogens have been implicated in the etiology of breast cancer for a long time. It has been stated that long-term exposure to estrogens is associated with a higher incidence of breast cancer, since estradiol (E2) stimulates breast cell growth; however, its effect on DNA damage/repair is only starting to be investigated. Recent studies have documented that estrogens are able to modify the DNA damage response (DDR) and DNA repair mechanisms. On the other hand, it has been proposed that DDR machinery can be altered by estrogen signaling pathways, that can be related to cancer progression and chemoresistance. We have demonstrated that E2 promotes c-Src activation and breast cancer cell motility, through a non-genomic pathway. This review discusses scientific evidence supporting this non-genomic mechanism where estrogen modifies the DNA repair pathways, and its relationship to potential causes of chemoresistance.

scholarly journals Potential miRNAs for miRNA-Based Therapeutics in Breast Cancer

2020 ◽  
Vol 6 (3) ◽  
pp. 29
Author(s):  
Jun Sheng Wong ◽  
Yoke Kqueen Cheah
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Cancer Recurrence ◽  
Mirna Biogenesis ◽  
In Vivo Models ◽  
Cellular Processes ◽  
Non Coding Rnas ◽  
Tumor Suppressor Mirnas

MicroRNAs (miRNAs) are small non-coding RNAs that can post-transcriptionally regulate the genes involved in critical cellular processes. The aberrant expressions of oncogenic or tumor suppressor miRNAs have been associated with cancer progression and malignancies. This resulted in the dysregulation of signaling pathways involved in cell proliferation, apoptosis and survival, metastasis, cancer recurrence and chemoresistance. In this review, we will first (i) provide an overview of the miRNA biogenesis pathways, and in vitro and in vivo models for research, (ii) summarize the most recent findings on the roles of microRNAs (miRNAs) that could potentially be used for miRNA-based therapy in the treatment of breast cancer and (iii) discuss the various therapeutic applications.

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