Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-42781
PROVIDER: PRJNA183127 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:A Splice Variant of HER2 Activates Key Signaling Cascades and Evokes Mammary Tumors and Metastases
2025-01-24 | E-GEOD-42781 | ExpressionAtlas
Project description:The Epidermal Growth Factor Receptor 2 (ERBB2 or HER2) is amplified and overexpressed in approximately 20% of invasive breast cancers and is associated with metastasis and poor prognosis. Here we describe the role of a constitutively active splice variant of HER2 (Delta-HER2) in human mammary epithelial cells. Overexpression of Delta-HER2 in human mammary cells decreased apoptosis and increased proliferation and expression of epithelial-to-mesenchymal markers. It also induced invasion in three-dimensional cultures and promoted tumorigenicity and metastasis in vivo. In contrast, similar overexpression of wild-type HER2 failed to evoke the same effects. Unbiased protein-tyrosine phosphorylation profiling revealed a significant increase in phosphorylation of several key signaling proteins upon Delta-HER2 expression, some of which not previously shown to belong to the HER2 pathway. In addition, microarray analysis revealed the expression of a set of genes specifically associated with Delta-HER2 expression. We found those genes to be highly expressed in ER-negative, high grade and metastatic primary breast tumors. Altogether, these results provide new insights into the function of a tumorigenic splice variant of HER2 and the signaling cascade deriving from its activity RNA was extracted from MCF10A expressing empty vector, WT-HER2 or Delta-HER2 (n=3).
2013-10-22 | E-GEOD-42781 | biostudies-arrayexpress
Project description:The Epidermal Growth Factor Receptor 2 (ERBB2 or HER2) is amplified and overexpressed in approximately 20% of invasive breast cancers and is associated with metastasis and poor prognosis. Here we describe the role of a constitutively active splice variant of HER2 (Delta-HER2) in human mammary epithelial cells. Overexpression of Delta-HER2 in human mammary cells decreased apoptosis and increased proliferation and expression of epithelial-to-mesenchymal markers. It also induced invasion in three-dimensional cultures and promoted tumorigenicity and metastasis in vivo. In contrast, similar overexpression of wild-type HER2 failed to evoke the same effects. Unbiased protein-tyrosine phosphorylation profiling revealed a significant increase in phosphorylation of several key signaling proteins upon Delta-HER2 expression, some of which not previously shown to belong to the HER2 pathway. In addition, microarray analysis revealed the expression of a set of genes specifically associated with Delta-HER2 expression. We found those genes to be highly expressed in ER-negative, high grade and metastatic primary breast tumors. Altogether, these results provide new insights into the function of a tumorigenic splice variant of HER2 and the signaling cascade deriving from its activity
2013-10-22 | GSE42781 | GEO
Project description:d16HER2 is a splice variant of HER2 receptor characterized by a significant tumor aggressiveness. We derived primary tumor cell lines from spontaneous tumors grown in mice transgenic respectively for human d16 (MI6 and MI7 cell lines) and WT HER2 isoforms (WTHER2_1 and WTHER2_2). To analyze the molecular mechanisms underlying the higher tumorigenicity of d16HER2 than that of WTHER2, we conducted gene expression profiling analysis of these cell lines.
2016-12-31 | GSE67300 | GEO
Project description:We studied cell lines derived from two transgenic mammary tumors driven by human HER2 that showed different dynamics of HER2 status. MamBo89 (HER2 stable) cell line displayed high and stable HER2 expression, which was maintained upon in vivo passages, whereas MamBo43 (HER2 labile) cell line gave rise to HER2-negative tumors, from which MamBo38 (HER2 loss) cell line was derived. MamBo cell lines were established from mammary tumors of FVBhuHER2 virgin female mice.
2021-11-30 | GSE181468 | GEO
Project description:Purpose: There is an unmet clinical need for biomarkers to identify breast cancer patients who are at increased risk of developing brain metastases. The objective is to identify gene signatures and biological pathways associated with HER2+ brain metastasis. Experimental Design: Gene expression of 19 HER2+ breast cancer brain metastases was compared with HER2+ nonmetastatic primary tumors. Gene Set Enrichment Analysis was used to identify a signature, which was evaluated for correlation with BRCA1 mutation status and clinical outcome using published microarray datasets and for correlation with pharmacological inhibition by a PARP inhibitor and temozolomide using published microarray datasets of breast cancer cell lines. Results: A BRCA1 Deficient-Like (BD-L) gene signature is significantly correlated with HER2+ metastases in both our and an independent cohort. BD-L signature is enriched in BRCA1 mutation carrier primary tumors and HER2-/ER- sporadic tumors, but high values are found in a subset of ER+ and HER2+ tumors. Elevated BD-L signature in primary tumors is associated with increased risk of overall relapse, brain relapse, and decreased survival. The BD-L signature correlates with pharmacologic response to PARP inhibitor and temozolomide in two independent microarray datasets, and the signature outperformed four published gene signatures of BRCA1/2 deficiency. Conclusions: The BD-L signature is enriched in breast cancer brain metastases and identifies a subset of primary tumors with increased propensity for brain metastasis. Furthermore, this signature may serve as a biomarker to identify sporadic breast cancer patients who could benefit from a therapeutic combination of PARP inhibitor and temozolomide. Gene expression of 19 HER2+ human breast cancer brain metastases was compared with gene expression of 19 HER2+ nonmetastatic primary human breast tumors.
2014-04-24 | E-GEOD-43837 | biostudies-arrayexpress
Project description:Cancer-associated fibroblasts (CAF) are part of the tumor microenvironment that enable cancer cells to establish metastases, but the mechanisms of these interactions are not fully known. Herein, we identify a novel paracrine mechanism in which CAF-secreted asporin (ASPN) activates ErbB signaling and subsequent migration of adjacent metastatic prostate cancer cells. Our data support that ASPN binds directly to HER3 to induce HER2/HER3 heterodimerization and activation of the PI3-kinase and MAP-kinase pathways. Genetic and therapeutic inhibition of HER2/HER3 ablated ASPN-induced signaling and migration. Small molecule and antibody-drug conjugates targeting HER2/HER3 demonstrated efficacy in vitro, with near complete resolution of tumors in vivo. Clinically, over 50% of human prostate cancer metastases show expression of HER2/HER3, along with ASPN expressing CAF. Collectively, these findings support ASPN functions as a HER3 ligand to induce cellular migration which can be targeted with anti-HER2/HER3 therapies, highlighting the potential clinical benefit for patients with metastatic prostate cancer.
2025-06-25 | GSE271579 | GEO
Project description:Cancer-associated fibroblasts (CAF) are part of the tumor microenvironment that enable cancer cells to establish metastases, but the mechanisms of these interactions are not fully known. Herein, we identify a novel paracrine mechanism in which CAF-secreted asporin (ASPN) activates ErbB signaling and subsequent migration of adjacent metastatic prostate cancer cells. Our data support that ASPN binds directly to HER3 to induce HER2/HER3 heterodimerization and activation of the PI3-kinase and MAP-kinase pathways. Genetic and therapeutic inhibition of HER2/HER3 ablated ASPN-induced signaling and migration. Small molecule and antibody-drug conjugates targeting HER2/HER3 demonstrated efficacy in vitro, with near complete resolution of tumors in vivo. Clinically, over 50% of human prostate cancer metastases show expression of HER2/HER3, along with ASPN expressing CAF. Collectively, these findings support ASPN functions as a HER3 ligand to induce cellular migration which can be targeted with anti-HER2/HER3 therapies, highlighting the potential clinical benefit for patients with metastatic prostate cancer.
2025-06-25 | GSE271742 | GEO
Project description:Cancer-associated fibroblasts (CAF) are part of the tumor microenvironment that enable cancer cells to establish metastases, but the mechanisms of these interactions are not fully known. Herein, we identify a novel paracrine mechanism in which CAF-secreted asporin (ASPN) activates ErbB signaling and subsequent migration of adjacent metastatic prostate cancer cells. Our data support that ASPN binds directly to HER3 to induce HER2/HER3 heterodimerization and activation of the PI3-kinase and MAP-kinase pathways. Genetic and therapeutic inhibition of HER2/HER3 ablated ASPN-induced signaling and migration. Small molecule and antibody-drug conjugates targeting HER2/HER3 demonstrated efficacy in vitro, with near complete resolution of tumors in vivo. Clinically, over 50% of human prostate cancer metastases show expression of HER2/HER3, along with ASPN expressing CAF. Collectively, these findings support ASPN functions as a HER3 ligand to induce cellular migration which can be targeted with anti-HER2/HER3 therapies, highlighting the potential clinical benefit for patients with metastatic prostate cancer.
2025-06-25 | GSE271740 | GEO
Project description:Cancer-associated fibroblasts (CAF) are part of the tumor microenvironment that enable cancer cells to establish metastases, but the mechanisms of these interactions are not fully known. Herein, we identify a novel paracrine mechanism in which CAF-secreted asporin (ASPN) activates ErbB signaling and subsequent migration of adjacent metastatic prostate cancer cells. Our data support that ASPN binds directly to HER3 to induce HER2/HER3 heterodimerization and activation of the PI3-kinase and MAP-kinase pathways. Genetic and therapeutic inhibition of HER2/HER3 ablated ASPN-induced signaling and migration. Small molecule and antibody-drug conjugates targeting HER2/HER3 demonstrated efficacy in vitro, with near complete resolution of tumors in vivo. Clinically, over 50% of human prostate cancer metastases show expression of HER2/HER3, along with ASPN expressing CAF. Collectively, these findings support ASPN functions as a HER3 ligand to induce cellular migration which can be targeted with anti-HER2/HER3 therapies, highlighting the potential clinical benefit for patients with metastatic prostate cancer.
2025-06-25 | GSE271739 | GEO