scholarly journals Semaphorin signaling via MICAL3 induces symmetric cell division to expand breast cancer stem-like cells

2018 ◽  
Vol 116 (2) ◽  
pp. 625-630 ◽  
Author(s):  
Kana Tominaga ◽  
Hiroshi Minato ◽  
Takahiko Murayama ◽  
Asako Sasahara ◽  
Tatsunori Nishimura ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Breast Cancer Patients ◽  
Asymmetric Cell Divisions ◽  
Symmetric Division ◽  
Cell Divisions ◽  
Tumor Sphere ◽  
Neuropilin 1 ◽  
Niche Factor ◽  
Sphere Formation

Cancer stem-like cells (CSCs) are expanded in the CSC niche by increased frequency of symmetric cell divisions at the expense of asymmetric cell divisions. The symmetric division of CSCs is important for the malignant properties of cancer; however, underlying molecular mechanisms remain largely elusive. Here, we show a cytokine, semaphorin 3 (Sema3), produced from the CSC niche, induces symmetric divisions of CSCs to expand the CSC population. Our findings indicate that stimulation with Sema3 induced sphere formation in breast cancer cells through neuropilin 1 (NP1) receptor that was specifically expressed in breast CSCs (BCSCs). Knockdown of MICAL3, a cytoplasmic Sema3 signal transducer, greatly decreased tumor sphere formation and tumor-initiating activity. Mechanistically, Sema3 induced interaction among MICAL3, collapsin response mediator protein 2 (CRMP2), and Numb. It appears that activity of MICAL3 monooxygenase (MO) stimulated by Sema3 is required for tumor sphere formation, interaction between CRMP2 and Numb, and accumulation of Numb protein. We found that knockdown of CRMP2 or Numb significantly decreased tumor sphere formation. Moreover, MICAL3 knockdown significantly decreased Sema3-induced symmetric divisions in NP1/Numb-positive BCSCs and increased asymmetric division that produces NP1/Numb negative cells without stem-like properties. In addition, breast cancer patients with NP1-positive cancer tissues show poor prognosis. Therefore, the niche factor Sema3-stimulated NP1/MICAL3/CRMP2/Numb axis appears to expand CSCs at least partly through increased frequency of MICAL3-mediated symmetric division of CSCs.

Neuropilin-1 is expressed by breast cancer stem-like cells and is linked to NF-κB activation and tumor sphere formation

2012 ◽  
Vol 425 (4) ◽  
pp. 775-780 ◽  
Author(s):  
Yelena Glinka ◽  
Nada Mohammed ◽  
Venkateswaran Subramaniam ◽  
Serge Jothy ◽  
Gérald J. Prud’homme
Keyword(s):  
Breast Cancer ◽  
Tumor Sphere ◽  
Neuropilin 1 ◽  
Sphere Formation

Role of Phytochemicals in the Treatment of Breast Cancer: Natural Swords battling Cancer Cells

2021 ◽  
Vol 16 ◽  
Author(s):  
Rajni Sawanny ◽  
Sheersha Pramanik ◽  
Unnati Agarwal
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Low Cost ◽  
Epigallocatechin Gallate ◽  
Cancer Therapeutics ◽  
Treatment Modalities ◽  
Breast Cancer Patients ◽  
Scientific Validity ◽  
Phytochemical Study ◽  
Treat Breast Cancer

: Breast cancer is the most common type of malignancy among ladies (around 30% of newly diagnosed patients every year). To date, various modern treatment modalities for breast cancer, such as radiotherapy, surgical method, hormonal therapy, and chemotherapeutic drug utilisation, are available. However, adverse drug reactions, therapeutic resistance, metastasis, or cancer reoccurrence chances remain the primary causes of mortality for breast cancer patients. To overcome all the potential drawbacks, we need to investigate novel techniques and strategies previously not considered and treat breast cancer effectively with safety and efficacy. For centuries, we utilise phytochemicals to treat various diseases because of their safety, low-cost & least or no side effects. Recently, naturally produced phytochemicals gain immense attention as potential breast cancer therapeutics because of their ideal characteristics; for instance, they operate via modulating molecular pathways associated with cancer growth and progression. The primary mechanism involves inhibition of cell proliferation, angiogenesis, migration, invasion, increasing anti-oxidant status, initiation of the arrest of the cell cycle, and apoptosis. Remedial viability gets effectively enhanced when phytochemicals work as adjuvants with chemotherapeutic drugs. This comprehensive review revolves around the latest chemopreventive, chemotherapeutic, and chemoprotective treatments with their molecular mechanisms to treat breast cancer by utilising phytochemicals such as vinca alkaloids, resveratrol, curcumin, paclitaxel, silibinin, quercetin, genistein and epigallocatechin gallate. The authors wish to extend the field of phytochemical study for its scientific validity and its druggability.

Regulation of the breast cancer stem cell phenotype by hypoxia-inducible factors

2015 ◽  
Vol 129 (12) ◽  
pp. 1037-1045 ◽  
Author(s):  
Gregg L. Semenza
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Primary Tumour ◽  
Tumour Microenvironment ◽  
Cell Phenotype ◽  
Breast Cancer Patients ◽  
Hypoxia Inducible Factors ◽  
Cancer Stem Cell Phenotype ◽  
Response To Chemotherapy ◽  
Small Subpopulation

The small subpopulation of breast cancer cells that possess the capability for self-renewal and formation of secondary tumours that recapitulate the heterogeneity of the primary tumour are referred to as tumour-initiating cells or BCSCs (breast cancer stem cells). The hypoxic tumour microenvironment and chemotherapy actively induce the BCSC phenotype. HIFs (hypoxia-inducible factors) are required and molecular mechanisms by which they promote the BCSC phenotype have recently been delineated. HIF inhibitors block chemotherapy-induced enrichment of BCSCs, suggesting that their use may improve the response to chemotherapy and increase the survival of breast cancer patients.

scholarly journals ASPH-notch Axis guided Exosomal delivery of Prometastatic Secretome renders breast Cancer multi-organ metastasis

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Qiushi Lin ◽  
Xuesong Chen ◽  
Fanzheng Meng ◽  
Kosuke Ogawa ◽  
Min Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Ductal Carcinoma ◽  
Disease Free Survival ◽  
Normal Adult ◽  
Luciferase Reporter ◽  
Breast Cancer Patients ◽  
Long Distance ◽  
Premetastatic Niche

Abstract Background Aspartate β-hydroxylase (ASPH) is silent in normal adult tissues only to re-emerge during oncogenesis where its function is required for generation and maintenance of malignant phenotypes. Exosomes enable prooncogenic secretome delivering and trafficking for long-distance cell-to-cell communication. This study aims to explore molecular mechanisms underlying how ASPH network regulates designated exosomes to program development and progression of breast cancer. Methods Stable cell lines overexpressing or knocking-out of ASPH were established using lentivirus transfection or CRISPR-CAS9 systems. Western blot, MTT, immunofluorescence, luciferase reporter, co-immunoprecipitation, 2D/3-D invasion, tube formation, mammosphere formation, immunohistochemistry and newly developed in vitro metastasis were applied. Results Through physical interactions with Notch receptors, ligands (JAGs) and regulators (ADAM10/17), ASPH activates Notch cascade to provide raw materials (especially MMPs/ADAMs) for synthesis/release of pro-metastatic exosomes. Exosomes orchestrate EMT, 2-D/3-D invasion, stemness, angiogenesis, and premetastatic niche formation. Small molecule inhibitors (SMIs) of ASPH’s β-hydroxylase specifically/efficiently abrogated in vitro metastasis, which mimics basement membrane invasion at primary site, intravasation/extravasation (transendothelial migration), and colonization/outgrowth at distant sites. Multiple organ-metastases in orthotopic and tail vein injection murine models were substantially blocked by a specific SMI. ASPH is silenced in normal adult breast, upregulated from in situ malignancies to highly expressed in invasive/advanced ductal carcinoma. Moderate-high expression of ASPH confers more aggressive molecular subtypes (TNBC or Her2 amplified), early recurrence/progression and devastating outcome (reduced overall/disease-free survival) of breast cancer. Expression profiling of Notch signaling components positively correlates with ASPH expression in breast cancer patients, confirming that ASPH-Notch axis acts functionally in breast tumorigenesis. Conclusions ASPH-Notch axis guides particularly selective exosomes to potentiate multifaceted metastasis. ASPH’s pro-oncogenic/pro-metastatic properties are essential for breast cancer development/progression, revealing a potential target for therapy.

Genomic heritage of sentinel lymph node metastases: Implications for clinical management of breast cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 571-571
Author(s):  
D. L. Ellsworth ◽  
R. E. Ellsworth ◽  
T. E. Becker ◽  
B. Deyarmin ◽  
H. L. Patney ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Lymph Node Metastases ◽  
Molecular Mechanisms ◽  
Breast Cancer Patients ◽  
Sentinel Nodes ◽  
Axillary Nodes ◽  
Node Metastases

571 Background: Sentinel lymph node (SLN) biopsy status is a key prognostic factor for breast cancer patients. Sentinel nodes are believed to receive early disseminating cells from the primary tumor, but little is known about the origin of metastases colonizing the sentinel nodes. We used allelic imbalance (AI) to examine genomic relationships among metastases in the sentinel and non-sentinel axillary lymph nodes from complete axillary dissections in 15 patients with lymph node positive breast cancer. Methods: Sentinel nodes were localized by standard scintigraphic and gamma probe techniques using 1.0 mCi technetium-99m sulfur colloid. Pathologically positive nodes were identified by H&E histology and immunohistochemistry. Primary breast tumors and metastases in sentinel and axillary nodes were isolated by laser microdissection. AI was assessed at 26 chromosomal regions and used to examine the timing and molecular mechanisms of metastatic spread to the sentinel and axillary nodes. Results: Overall AI frequencies were significantly higher (p<0.05) in primary breast tumors compared to lymph node metastases. A high level of discordance was observed in patterns and frequencies of AI events between metastases in the sentinel and non-sentinel axillary nodes. Phylogenetic analyses showed that 1) multiple genetically-divergent lineages of metastatic cells independently colonize the lymph nodes; 2) some lymph node metastases appeared to acquire metastatic potential early in tumorigenesis, while other metastases evolved later; and 3) importantly, lineages colonizing the sentinel nodes appeared to originate at different times and to progress by different molecular mechanisms. Conclusions: Genomic diversity and timing of metastatic nodal spread may be important factors in determining outcomes of breast cancer patients. Metastases colonizing the sentinel nodes appear to arise at different times during disease progression and may not be descendants of progenitor cells that colonize the lymph nodes early in tumorigenesis. Metastatic growth in the sentinel nodes thus may be a consequence of stimulating factors from the primary tumor that affect proliferation of previously disseminated cells rather than the timing of metastatic spread. No significant financial relationships to disclose.

scholarly journals MAP3K1 SNP rs889312 potential risk and MAP3K9 SNP rs11628333 menopause dependent association for breast cancer

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Samina Asghar Abbasi ◽  
Ruqia Mehmood Baig ◽  
Mehvish Naseer Ahmed ◽  
Muhammad Ismail ◽  
Rashida Khan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
South Asian ◽  
Molecular Mechanisms ◽  
Strong Association ◽  
Breast Cancer Patients ◽  
The South ◽  
Asian Region ◽  
Post Menopausal ◽  
South Asian Region

Abstract Objectives Breast cancer is the leading cause of mortality in today’s world. An alarming rise in cancer incidence has been observed in the South Asian region. The aberrant molecular mechanisms regulating cell proliferation and development contribute to cancer development. A better understanding of the detailed molecular mechanisms at genetic and epigenetic levels can help to treat breast cancer more efficiently. The present study is aimed to identify the possible association of MAP3K1 SNP rs889312 and MAP3K9 rs11628333 in breast cancer in the South Asian region. Materials and methods Female breast cancer patients were recruited in the study. DNA was isolated from the blood samples collected from the patients. PCR-RFLP was used for genotyping, and data analysis was done by SPSS software. Results Genotyping data for MAP3K1 SNPrs889312 showed statistically significant association with breast cancer, while MAP3K9 SNPrs11628333 showed characteristic association of rare allele heterozygote’s and homozygotes in pre and post-menopausal patients, respectively. Conclusion The study concludes a strong association of the rs889312 with breast cancer in the Pakistani population and a characteristic association of unique genotypes TC and CC in pre- and post-menopausal breast cancer patients. These findings can provide a ready tool as a breast cancer marker in south Asian populations.

scholarly journals Identification and Validation of a Five-gene Signature Associated with Overall Survival in Breast Cancer Patients

2020 ◽  
Author(s):  
Xiaolong Wang ◽  
Chen Li ◽  
Tong Chen ◽  
Hanwen Zhang ◽  
Ying Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Individual Treatment ◽  
Breast Cancer Patients ◽  
Internal Validation ◽  
Novel Biomarkers

Abstract Background Recent years, attributed to early detection and new therapies, the mortality rates of breast cancer (BC) decreased. Nevertheless, the global prevalence was still high and the underlying molecular mechanisms were remained largely unknown. The investigation of prognosis-related genes as the novel biomarkers for diagnosis and individual treatment had become an urgent demand for clinical practice. Methods Gene expression profiles and clinical information of breast cancer patients were downloaded from The Cancer Genome Atlas (TCGA) database and randomly divided into training (n = 514) and internal validation (n = 562) cohort by using a random number table. The differentially expressed genes (DEGs) were estimated by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In the training set, the gene signature was constructed by the least absolute shrinkage and selection operator (LASSO) method based on DEGs screened by R packages. The results were further tested in the internal validation cohort and the entire cohort. Moreover, functions of five genes were explored by MTT, Colony-Formation, scratch and transwell assays. Western blot analysis was used to explore the mechanisms. Results In the training cohort, a total of 2805 protein coding DEGs were acquired through comparing breast cancer tissues (n = 514) with normal tissues (n = 113). A risk score formula involving five novel prognostic associated biomarkers (EDN2, CLEC3B, SV2C, WT1 and MUC2) were then constructed by LASSO. The prognostic value of the risk model was further confirmed in the internal validation set and the entire set. To explore the biological functions of the selected genes, in vitro assays were performed, indicating that these novel biomarkers could markedly influence breast cancer progression. Conclusion We established a predictive five-gene signature, which could be helpful for prognosis assessment and personalized management in breast cancer patients.

The gene expression profiling gives an in-depth insight of breast cancer heterogeneity, better than a single protein or gene expression. It is time to include it in the daily routine

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Molecular Mechanisms ◽  
Deep Understanding ◽  
Daily Routine ◽  
Breast Cancer Patients ◽  
Clinical Value ◽  
Single Protein ◽  
Or Gene ◽  
Better Than

Cancer treatments used to be a one-size-fits-all strategy; nowadays, decisions are based on the specific molecular pathology of each patient's tumor. Personalized medicine is based on a deep understanding of disease mechanisms and the use of customized drugs to target those mechanisms, with the potential of greater treatment efficacy. The transcriptome revolution offered molecular insight into some carcinogenic pathways. This study has led to the conclusion that the four most common IHC biomarkers (HER2, ER, PR, and Ki67) can not accurately represent the complexity of breast cancer sickness. The GEP gives an in-depth insight of illness heterogeneity, better than a single protein or gene expression. Development of a framework and rigorous criteria have caused delays in the application of the GEP in clinical and regulatory contexts. There was also the issue of researchers and physicians becoming distracted by external pressures and being pulled in other directions.Clinicians use the classification approach for better judgements about breast cancer. Whether intrinsic subtyping has enough clinical value to merit including GEP as a supplemental test alongside IHC testing in international guidelines is still debated. Even though intrinsic subtyping has an influence on current clinical trial designs, it is relevant to biomarker research. It is time to include it in the daily routine of breast cancer sufferers. a continuing emphasis on refining this classification Nucleotide variations and their underlying molecular mechanisms, and the effect of the immune system on treatment outcome, will inform novel therapeutic regimes. Combining biological processes, as a result, would probably probably be included in the implementation of tailored therapeutic paradigms in breast cancer patients.

scholarly journals Single-Cell Tracking of Breast Cancer Cells Enables Prediction of Sphere Formation from Early Cell Divisions

iScience ◽  
2018 ◽  
Vol 8 ◽  
pp. 29-39 ◽  
Author(s):  
Patrick C. Bailey ◽  
Rachel M. Lee ◽  
Michele I. Vitolo ◽  
Stephen J.P. Pratt ◽  
Eleanor Ory ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cell Tracking ◽  
Cell Divisions ◽  
Sphere Formation

scholarly journals miR-338-3p Is Regulated by Estrogens through GPER in Breast Cancer Cells and Cancer-Associated Fibroblasts (CAFs)

Cells ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 203 ◽  
Author(s):  
Adele Vivacqua ◽  
Anna Sebastiani ◽  
Anna Miglietta ◽  
Damiano Rigiracciolo ◽  
Francesca Cirillo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Cancer Associated Fibroblasts ◽  
Breast Cancer Patients ◽  
Expression Of Genes ◽  
Taqman Array

Estrogens acting through the classic estrogen receptors (ERs) and the G protein estrogen receptor (GPER) regulate the expression of diverse miRNAs, small sequences of non-coding RNA involved in several pathophysiological conditions, including breast cancer. In order to provide novel insights on miRNAs regulation by estrogens in breast tumor, we evaluated the expression of 754 miRNAs by TaqMan Array in ER-negative and GPER-positive SkBr3 breast cancer cells and cancer-associated fibroblasts (CAFs) upon 17β-estradiol (E2) treatment. Various miRNAs were regulated by E2 in a peculiar manner in SkBr3 cancer cells and CAFs, while miR-338-3p displayed a similar regulation in both cell types. By METABRIC database analysis we ascertained that miR-338-3p positively correlates with overall survival in breast cancer patients, according to previous studies showing that miR-338-3p may suppress the growth and invasion of different cancer cells. Well-fitting with these data, a miR-338-3p mimic sequence decreased and a miR-338-3p inhibitor sequence rescued the expression of genes and the proliferative effects induced by E2 through GPER in SkBr3 cancer cells and CAFs. Altogether, our results provide novel evidence on the molecular mechanisms by which E2 may regulate miR-338-3p toward breast cancer progression.

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