Similar Datasets
Project description:Hepsin, a type II transmembrane serine protease, is commonly overexpressed in prostate and breast cancer. The hepsin protein is stabilized by the Ras-MAPK pathway, and downstream, this protease regulates the degradation of extracellular matrix components and activates growth factor pathways, such as hepatocyte growth factor and transforming growth factor beta (TGFβ) pathway. However, how exactly active hepsin promotes cell proliferation machinery to sustain tumor growth is not fully understood. Here, we show that genetic deletion of Hpn in a WAP-Myc model of aggressive MYC-driven breast cancer inhibits tumor growth in the primary syngrafted sites and the growth of disseminated tumors in the lungs. The suppression of tumor growth upon loss of hepsin was accompanied by downregulation of TGFβ and EGFR signaling together with a reduction in EGFR protein levels. We further demonstrate in 3D cultures of patient-derived breast cancer explants that neutralizing antibodies and small-molecule inhibitors of hepsin can be used to mitigate the hepsin-induced TGFβ signaling and reduce EGFR protein levels.The study demonstrates a role for hepsin as a regulator of cell proliferation and tumor growth through TGFβ and EGFR pathways, warranting consideration of hepsin as a potential indirect upstream target for therapeutic inhibition of TGFβ and EGFR pathways in cancer.
2023-10-30 | GSE245265 | GEO
Project description:To investigate the role FGF signaling in limb bud development we inhibited FGF signaling in limb bud explants by treatment with 5µM SU5402, an FGFR inhibitor, or DMSO as control. We then performed mRNA sequencing on RNA collected after 48h of treatment to analyse the effect on gene expression.
2023-08-24 | GSE223444 | GEO
Project description:To test if ectopic overexpression of hepsin (TMPRSS1) induces TGFβ signaling in the context of tumorigenesis, we made use of a previously published tumor syngraft model of Myc-driven breast cancer (Partanen et al., 2012 PMID: 22308451). Wap-Myc mammary tumor cells, which express high Myc levels, were isolated from donor mice, transduced with the pIND21-HPN lentiviral construct that allows doxycycline (DOX)-induced hepsin overexpression, and subsequentially transplanted into recipient mice. Consistent with the notion that hepsin promotes TGFβ signaling, western blot analysis revealed increased phospho-Smad2/3 and upregulation of the TGFβ signaling downstream target SNAIL in Wap-Myc tumors with DOX-induced hepsin overexpression compared to control (-DOX) tumors. RNAseq analysis of these tumors provided additional evidence for TGFβ pathway upregulation by hepsin as the most significantly upregulated gene signatures corresponded to the TGFβ signaling pathway. The largest cluster of gene signatures affected by hepsin overexpression, however, was related to the ECM and integrins.
2021-08-04 | GSE164510 | GEO
Project description:We have worked on skin explants and activated T cells locally with a CD3 antibody, whole biopsies were activated, then epidermal and dermal RNA was sequenced. Sequencing was performed by BGI (Hong Kong) as well as the group analysis.
2018-03-16 | GSE103489 | GEO
Project description:The role of PGC1alpha in breast cancer lung metastasis is largely unknown. We used expression data from lung metastatic explants overexpressing PGC1alpha or control, treated with phenformin to understand global gene expression changes which occur in a PGC1alpha context and under phenformin treatment. We used expression data to understand the pathways and genes that may lead to lung metastasis in a PGC1alpha overexpression setting.
2017-09-06 | GSE99556 | GEO
Project description:chick intermediate neural explants
| PRJEB5921 | ENA
Project description:The aim of the experiment was to investigate the effect of TVB-3166 treatment in primary patient-derived breast tumor explants. RNA sequencing was performed in response to treatment with TVB-3166 or vehicle control. RNA sequencing analyses revealed that TVB significantly altered the mRNA expression of 219 genes as compared to the control.
2022-12-21 | GSE166018 | GEO
Project description:Transforming growth factor beta (TGFβ) is a multifunctional cytokine with a well-established role in mammary gland development and both oncogenic and tumor-suppressive functions. The extracellular matrix (ECM) indirectly regulates TGFβ activity by acting as a storage compartment of latent TGFβ, but how TGFβ is released from the ECM via proteolytic mechanisms remains largely unknown. In this study, we demonstrate that hepsin, a type II transmembrane protease overexpressed in 70% of breast tumors, promotes canonical TGFβ signaling through the release of latent TGFβ from the ECM-storage compartment. Mammary glands in hepsin CRISPR knock-out mice showed reduced TGFβ signaling and increased epithelial branching, accompanied by increased levels of fibronectin and latent TGFβ1, while overexpression of hepsin in mammary tumors increased TGFβ signaling. Cell-free and cell-based experiments showed that hepsin is capable of direct proteolytic cleavage of fibronectin but not latent TGFβ and, importantly, that the ability of hepsin to activate TGFβ signaling is dependent on fibronectin. Altogether, this study demonstrates a role for hepsin as a regulator of the TGFβ pathway in the mammary gland via a novel mechanism involving proteolytic downmodulation of fibronectin.
2021-08-04 | GSE164509 | GEO
Project description:Animal pole tissue explants were dissected from either untreated embryos or embryos injected with 1 ng of Notch Intracellular Domain RNA (NICD) at the two cell stage. Tissue explants were dissected and cultured until sibling embryos reached embryonic stage 20. Each array hybridization represents a biological replicate containing approximately 100 tissue explants. Expression profiles were determined using Affymetrix Xenopus Genechip 1 arrays. Experiment Overall Design: 4 untreated pooled explants, 2 NICD treated explants
2008-06-13 | E-GEOD-5564 | biostudies-arrayexpress
Project description:Breast tumorigenesis involves modulation of gene expression. We used microarrays to detail the global program of gene expression underlying breast tumorigenesis. Three examples of stage I breast tumor and 3 samples of breast reduction mammoplasty tissue were expanded as explant cultures for RNA extraction and hybridization to Affymetrix microarrays.
2010-11-17 | E-GEOD-25407 | biostudies-arrayexpress