Asperolide A prevents bone metastatic breast cancer via the PI3K/AKT/mTOR/c‐Fos/NFATc1 signaling pathway

Understanding the molecular pathways that contribute to the development of metastatic breast cancer invasion and metastasis to brain is needed to improve the clinical utility of novel agents, and to predict the success of targeted personalized therapy based on tumor-specific mutations. Little is known about the clinical significance of HER2/ERK1/2/MMP-9 signaling pathway in breast cancer. We performed Global exon array to study the expression of ERK1/2/MMP-9 signaling pathway in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of ERK1/2/MMP-9 proteins in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells.

Download Full-text

Nucleotide de novo synthesis increases breast cancer stemness and metastasis via cGMP-PKG-MAPK signaling pathway

PLoS Biology ◽

10.1371/journal.pbio.3000872 ◽

2020 ◽

Vol 18 (11) ◽

pp. e3000872

Author(s):

Yajing Lv ◽

Xiaoshuang Wang ◽

Xiaoyu Li ◽

Guangwei Xu ◽

Yuting Bai ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Breast Cancer Cells ◽

Cancer Metastasis ◽

De Novo ◽

Metastatic Breast ◽

Metabolic Reprogramming ◽

De Novo Synthesis

Metabolic reprogramming to fulfill the biosynthetic and bioenergetic demands of cancer cells has aroused great interest in recent years. However, metabolic reprogramming for cancer metastasis has not been well elucidated. Here, we screened a subpopulation of breast cancer cells with highly metastatic capacity to the lung in mice and investigated the metabolic alternations by analyzing the metabolome and the transcriptome, which were confirmed in breast cancer cells, mouse models, and patients’ tissues. The effects and the mechanisms of nucleotide de novo synthesis in cancer metastasis were further evaluated in vitro and in vivo. In our study, we report an increased nucleotide de novo synthesis as a key metabolic hallmark in metastatic breast cancer cells and revealed that enforced nucleotide de novo synthesis was enough to drive the metastasis of breast cancer cells. An increased key metabolite of de novo synthesis, guanosine-5'-triphosphate (GTP), is able to generate more cyclic guanosine monophosphate (cGMP) to activate cGMP-dependent protein kinases PKG and downstream MAPK pathway, resulting in the increased tumor cell stemness and metastasis. Blocking de novo synthesis by silencing phosphoribosylpyrophosphate synthetase 2 (PRPS2) can effectively decrease the stemness of breast cancer cells and reduce the lung metastasis. More interestingly, in breast cancer patients, the level of plasma uric acid (UA), a downstream metabolite of purine, is tightly correlated with patient’s survival. Our study uncovered that increased de novo synthesis is a metabolic hallmark of metastatic breast cancer cells and its metabolites can regulate the signaling pathway to promote the stemness and metastasis of breast cancer.

Download Full-text

The expression pattern of members of the EGFR signaling pathway and its relation with the duration of response in metastatic breast cancer (BC) patients (pts) treated with endocrine therapy (ET)

Journal of Clinical Oncology ◽

10.1200/jco.2004.22.14_suppl.3170 ◽

2004 ◽

Vol 22 (14_suppl) ◽

pp. 3170-3170

Author(s):

G. Atalay ◽

V. Durbecq ◽

D. Larsimont ◽

G. Rouas ◽

A. Di Leo ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Endocrine Therapy ◽

Signaling Pathway ◽

Expression Pattern ◽

Metastatic Breast ◽

Egfr Signaling ◽

Egfr Signaling Pathway ◽

Duration Of Response

Download Full-text

Wnt/β-catenin signaling pathway and thioredoxin-interacting protein (TXNIP) mediate the “glucose sensor” mechanism in metastatic breast cancer-derived cells MDA-MB-231

Journal of Cellular Physiology ◽

10.1002/jcp.22757 ◽

2011 ◽

Vol 227 (2) ◽

pp. 578-586 ◽

Cited By ~ 10

Author(s):

Sergio Vaira ◽

Ellen Friday ◽

Keith Scott ◽

Steven Conrad ◽

Francesco Turturro

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Signaling Pathway ◽

Glucose Sensor ◽

Metastatic Breast ◽

Interacting Protein ◽

Thioredoxin Interacting Protein

Download Full-text

Heterogeneity in signaling pathway activity within primary and between primary and metastatic breast cancer

10.1101/2020.07.27.223834 ◽

2020 ◽

Author(s):

Márcia A. Inda ◽

Paul van Swinderen ◽

Anne van Brussel ◽

Cathy B. Moelans ◽

Wim Verhaegh ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Signaling Pathway ◽

Metastatic Breast ◽

Pi3k Pathway ◽

Pathway Activity ◽

Micro Scale ◽

Scale Heterogeneity ◽

Macro Scale ◽

Heterogeneity Analysis

AbstractBackgroundTargeted drug treatment aims to block tumor driving signaling pathways, and is generally based on analysis of one primary tumor (PT) biopsy. Phenotypic heterogeneity within primary and between primary and metastatic lesions was investigated.MethodsActivity of androgen and estrogen receptor, PI3K-FOXO, Hedgehog, TGFβ, and Wnt signaling pathways was measured in breast cancer samples using a novel mRNA-based assay platform. Macro-scale heterogeneity analysis was performed on multiple spatially distributed PT tissue blocks from 17 luminal A-like, 9 luminal B-like, and 9 ER-negative primary breast cancers; micro-scale heterogeneity analysis was performed on four “quadrant” samples of a single tissue block of respectively 9, 4, and 4 matched PT. Samples from 6 PT with matched lymph node (LN, n=23) and 9 PT with distant metastatic sites (DS, n=12) were analyzed. Statistical variance analysis was performed with linear mixed models. A “checkerboard” model was introduced to explain the observed heterogeneity in PT.ResultsWithin PT, macro-scale heterogeneity in signaling pathway activity was similar to micro-scale heterogeneity, with a possible exception of the PI3K pathway. Variation was significantly higher on microscale for Hedgehog and TGFβ pathways. While pathway activity scores correlated significantly between different locations in the PT, positive correlations decreased between PT and LN, and even more between PT and DS metastases, including the emergence of a negative correlation for the ER pathway.ConclusionWith a possible exception of the PI3K pathway, variation in signaling pathway activity within a single PT tissue block was generally representative for the whole PT, but not for DS or LN metastases. The higher variation in TGFβ and HH pathway activity on microscale suggested the presence of multiple small cancer cell clones. While analysis of multiple sub-samples of a single biopsy block may be sufficient to predict PT response to some targeted therapies, such as hormonal therapy, metastatic breast cancer treatment requires analysis of metastatic biopsies. The findings on phenotypic intra-tumor heterogeneity are compatible with currently emerging ideas on a Big Bang type of cancer evolution.

Download Full-text

Suppressions of metastatic breast cancer invasion and metastasis to brain/cross talk HER2/ERK1/2/MMP-9 signaling pathway

American Journal of BioMedicine ◽

10.18081/2333-5106/016-227-239 ◽

2016 ◽

Vol 4 (2) ◽

pp. 227-239

Author(s):

Yu-Chun Lin ◽

Dong-Qing Chin

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Signaling Pathway ◽

Metastatic Breast ◽

Cancer Invasion ◽

Breast Cancer Cell Lines ◽

Breast Cancers ◽

Invasion And Metastasis ◽

Matrigel Invasion ◽

Breast Cancer Invasion

Understanding the molecular pathways that contribute to the development of metastatic breast cancer invasion and metastasis to brain is needed to improve the clinical utility of novel agents, and to predict the success of targeted personalized therapy based on tumor-specific mutations. Little is known about the clinical significance of HER2/ERK1/2/MMP-9 signaling pathway in breast cancer. We performed Global exon array to study the expression of ERK1/2/MMP-9 signaling pathway in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of ERK1/2/MMP-9 proteins in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells.

Download Full-text