Invasion-mediating genes in breast cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Bjourson Anthony
PROVIDER: S-ECPF-GEOD-17889 | biostudies-other |
REPOSITORIES: biostudies-other
Similar Datasets
Project description:From the parental breast cancer cell line MCF7 (weakly invasive), we progressively selected hyperinvasive subclones. We compared the gene expression between the parental MCF7-I0 and the hyper-invasive cells MCF7-I6. We used Affymetrix U133 Plus 2 microarrays to detail the global programme of gene expression underlying weakly and highly invasive breast cancer cells derived from the human breast cancer cell line MCF7. The hyper-invasive subclones were selected using Matrigel invasion chambers as a model for the invasion process in vivo. The cells that invaded through the membrane were cultured and re-introduced into an additional invasion assay. This methodology was repeated to give rise to a subclone of MCF7 cells that had invaded six times; these were termed MCF7-I6 cells. The invasive capacity of MCF7-I6 cells was shown to be more than 11 times greater than the parental cells, which we denote as MCF7-I0. Thus, these hyper-invasive cells were present within the heterogeneous population, and we speculated that differences in gene expression between the MCF7-I6 cells and the parental cells MCF7-I0 may be involved in the invasion process.
2011-12-10 | E-GEOD-17889 | biostudies-arrayexpress
Project description:From the parental breast cancer cell line MCF7 (weakly invasive), we progressively selected hyperinvasive subclones. We compared the gene expression between the parental MCF7-I0 and the hyper-invasive cells MCF7-I6. We used Affymetrix U133 Plus 2 microarrays to detail the global programme of gene expression underlying weakly and highly invasive breast cancer cells derived from the human breast cancer cell line MCF7.
2011-12-10 | GSE17889 | GEO
Project description:Rab proteins play crucial roles in membrane trafficking. Some Rab proteins are implicated in cancer development through regulating protein sorting or degradation. In this study, we found that the expression of Rab26 is suppressed in the aggressive breast cancer cells as compared to the levels in non-invasive breast cancer cells. Over-expression of Rab26 inhibits cell migration and invasion, while Rab26 knockdown significantly promotes the migration and invasion of breast cancer cells. Rab26 reduces focal adhesion association of Src kinase and induces endosomal translocation of Src. Further experiments revealed that Rab26 mediates the autophagic degradation of phosphorylated Src through interacting with ATG16L1, consequently, resulting in the suppression of the migration and invasion ability of breast cancer cells.
| S-EPMC7969620 | biostudies-literature
Project description:Metastasis remains a significant challenge in treating cancer. A better understanding of the molecular mechanisms underlying metastasis is needed to develop more effective treatments. Here, we show that human breast tumor biomarker miR-30c regulates invasion by targeting the cytoskeleton network genes encoding twinfilin 1 (TWF1) and vimentin (VIM). Both VIM and TWF1 have been shown to regulate epithelial-to-mesenchymal transition. Similar to TWF1, VIM also regulates F-actin formation, a key component of cellular transition to a more invasive mesenchymal phenotype. To further characterize the role of the TWF1 pathway in breast cancer, we found that IL-11 is an important target of TWF1 that regulates breast cancer cell invasion and STAT3 phosphorylation. The miR-30c-VIM/TWF1 signaling cascade is also associated with clinical outcome in breast cancer patients.
| S-EPMC3583223 | biostudies-literature
Project description:Invasion and metastasis of aggressive breast cancer cells are the final and fatal steps during cancer progression. Clinically, there are still limited therapeutic interventions for aggressive and metastatic breast cancers available. Therefore, effective, targeted, and non-toxic therapies are urgently required. Id-1, an inhibitor of basic helix-loop-helix transcription factors, has recently been shown to be a key regulator of the metastatic potential of breast and additional cancers. We previously reported that cannabidiol (CBD), a cannabinoid with a low toxicity profile, down-regulated Id-1 gene expression in aggressive human breast cancer cells in culture. Using cell proliferation and invasion assays, cell flow cytometry to examine cell cycle and the formation of reactive oxygen species, and Western analysis, we determined pathways leading to the down-regulation of Id-1 expression by CBD and consequently to the inhibition of the proliferative and invasive phenotype of human breast cancer cells. Then, using the mouse 4T1 mammary tumor cell line and the ranksum test, two different syngeneic models of tumor metastasis to the lungs were chosen to determine whether treatment with CBD would reduce metastasis in vivo. We show that CBD inhibits human breast cancer cell proliferation and invasion through differential modulation of the extracellular signal-regulated kinase (ERK) and reactive oxygen species (ROS) pathways, and that both pathways lead to down-regulation of Id-1 expression. Moreover, we demonstrate that CBD up-regulates the pro-differentiation factor, Id-2. Using immune competent mice, we then show that treatment with CBD significantly reduces primary tumor mass as well as the size and number of lung metastatic foci in two models of metastasis. Our data demonstrate the efficacy of CBD in pre-clinical models of breast cancer. The results have the potential to lead to the development of novel non-toxic compounds for the treatment of breast cancer metastasis, and the information gained from these experiments broaden our knowledge of both Id-1 and cannabinoid biology as it pertains to cancer progression.
| S-EPMC3410650 | biostudies-literature
Project description:Background Breast cancer (BRCA) shows genetic, epigenetic, and phenotypic diversity. Methylation of N6-methyladenosine (m6A) affects the occurrence, development, and therapeutic efficacy of BRCA. However, the characteristics and prognostic value of m6A in BRCA remain unclear. We aimed to classify and construct a scoring system for the m6A regulatory gene in BRCA, and to explore its potential mechanisms. Methods In this study, we selected 23 m6A regulatory genes and analyzed their genetic variation in BRCA, including copy number variation (CNV) data, expression differences, mutations, gene types, and correlations between genes. Survival curves were drawn by the Kaplan-Meier method, and a log-rank P<0.05 was considered statistically significant. The partitioning around medoids (PAM) algorithm was used for molecular subtype analysis of m6A, single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to quantify the relative infiltration levels of various immune cell subgroups, and a scoring system was built based on principal component analysis (PCA). Results In BRCA, m6A regulatory gene mutation frequency is not high, while that of CNV mutation is high, which is related to gene expression and closely related to prognosis. In this study, we identified 3 different m6A subtypes, which are closely related to the level of immune cell infiltration. We further constructed an m6A score system, in which lower scores were correlated with low tumor mutation burden (TMB), later clinical staging, programmed cell death 1 ligand 1 (PD-L1) expression, and triple-negative breast cancer (TNBC). Conclusions This study highlights the diversity and complexity of the role of m6A in BRCA. The classification of BRCA based on the m6A regulatory gene can help us understand the characteristics of BRCA and help develop individualized immunotherapy regimens.
| S-EPMC8506726 | biostudies-literature
Project description:Introduction: Metastasis of breast cancer is the main cause of death in patients. Previous genome-wide studies have identified gene expression patterns correlated with cancer patient outcome, however these were mostly derived from whole tissue without respect to cell heterogeneity. In reality, only a small subpopulation of migratory and invasive cells inside the primary tumor is responsible for escaping and initiating dissemination and metastasis. When whole tissue is used for molecular profiling, the expression pattern of these cells is masked by the majority of the non-invasive tumor cells. Therefore, little information is available about the crucial early steps of the metastatic cascade: migration, invasion and entry of tumor cells into the systemic circulation. Method: In the past, we have developed an in vivo invasion assay which can capture specifically the highly motile tumor cells in the act of migrating inside living tumors (Wyckoff et al., 2004, Cancer Research). Here, we used this assay in orthotopic xenografts of human MDA-MB-231 breast cancer cells to selectively isolate the invasive cell subpopulation of the primary tumor. We then performed microarray analysis to compare the gene expression profile of these invading tumor cells to the average primary tumor cells. In this way, we derived a gene signature specific to breast cancer migration and invasion in vivo. Each sample of invasive (INV) and average primary tumor cells (APTC) was pooled from two tumor-bearing mice. RNA was extracted, made into cDNA, then amplified with the Clontech SMART amplification kit. Human reference RNA (Clontech) was amplified with identifical protocol. Each sample was then hybridized in a 28K Human cDNA microarray chip, custom printed from Albert Einstein College of Medicine (http://microarray1k.aecom.yu.edu/). Four replicates were used per group (Invasive vs. Average Primary Tumor).
| S-ECPF-GEOD-37733 | biostudies-other
Project description:Introduction: Metastasis of breast cancer is the main cause of death in patients. Previous genome-wide studies have identified gene expression patterns correlated with cancer patient outcome, however these were mostly derived from whole tissue without respect to cell heterogeneity. In reality, only a small subpopulation of migratory and invasive cells inside the primary tumor is responsible for escaping and initiating dissemination and metastasis. When whole tissue is used for molecular profiling, the expression pattern of these cells is masked by the majority of the non-invasive tumor cells. Therefore, little information is available about the crucial early steps of the metastatic cascade: migration, invasion and entry of tumor cells into the systemic circulation. Method: In the past, we have developed an in vivo invasion assay which can capture specifically the highly motile tumor cells in the act of migrating inside living tumors (Wyckoff et al., 2004, Cancer Research). Here, we used this assay in orthotopic xenografts of human MDA-MB-231 breast cancer cells to selectively isolate the invasive cell subpopulation of the primary tumor. We then performed microarray analysis to compare the gene expression profile of these invading tumor cells to the average primary tumor cells. In this way, we derived a gene signature specific to breast cancer migration and invasion in vivo. Each sample of invasive (INV) and average primary tumor cells (APTC) was pooled from two tumor-bearing mice. RNA was extracted, made into cDNA, then amplified with the Clontech SMART amplification kit. Human reference RNA (Clontech) was amplified with identifical protocol. Each sample was then hybridized in a 28K Human cDNA microarray chip, custom printed from Albert Einstein College of Medicine (http://microarray1k.aecom.yu.edu/). Four replicates were used per group (Invasive vs. Average Primary Tumor).
2012-09-05 | E-GEOD-37733 | biostudies-arrayexpress
Project description:Introduction: Metastasis of breast cancer is the main cause of death in patients. Previous genome-wide studies have identified gene expression patterns correlated with cancer patient outcome, however these were mostly derived from whole tissue without respect to cell heterogeneity. In reality, only a small subpopulation of migratory and invasive cells inside the primary tumor is responsible for escaping and initiating dissemination and metastasis. When whole tissue is used for molecular profiling, the expression pattern of these cells is masked by the majority of the non-invasive tumor cells. Therefore, little information is available about the crucial early steps of the metastatic cascade: migration, invasion and entry of tumor cells into the systemic circulation. Method: In the past, we have developed an in vivo invasion assay which can capture specifically the highly motile tumor cells in the act of migrating inside living tumors (Wyckoff et al., 2004, Cancer Research). Here, we used this assay in orthotopic xenografts of human MDA-MB-231 breast cancer cells to selectively isolate the invasive cell subpopulation of the primary tumor. We then performed microarray analysis to compare the gene expression profile of these invading tumor cells to the average primary tumor cells. In this way, we derived a gene signature specific to breast cancer migration and invasion in vivo.
2012-09-05 | GSE37733 | GEO
Project description:Breast cancers contain regions of intratumoral hypoxia in which reduced O(2) availability activates the hypoxia-inducible factors HIF-1 and HIF-2, which increase the transcription of genes encoding proteins that are required for many important steps in cancer progression. Recently, HIFs have been shown to play critical roles in the metastasis of breast cancer to the lungs through the transcriptional activation of genes encoding angiopoietin-like 4 and L1 cell adhesion molecule, which promote the extravasation of circulating cancer cells from the lung vasculature, and the lysyl oxidase family members LOX, LOXL2, and LOXL4, which promote invasion and metastatic niche formation. Digoxin, a drug that inhibits HIF-1 activity, blocks primary tumor growth, vascularization, invasion, and metastasis in ex vivo and in vivo assays.
| S-EPMC3449282 | biostudies-literature