Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA138495 | ENA |
REPOSITORIES: ENA
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Project description:Stress-induced phosphoprotein 1 (STIP1), a co-chaperone that organizes other chaperones- heat shock proteins (HSP), was recently shown to be secreted by human ovarian cancer cells to induce cell proliferation. In neuronal tissues, binding to prion protein was required for STIP1 to activate the ERK (extracellular regulated MAP kinase) signaling pathways. However, in this study, we found that STIP1 stimulated cell proliferation of ovarian cancer via a bone morphogenetic protein (BMP) signaling pathway, not through the prion-ERK pathway. The STIP1 binding to a BMP receptor, ALK2 (activin A receptor, type II-like kinase 2), was necessary and sufficient to stimulate cancer cell proliferation. The binding of STIP1 to ALK2 activated the SMAD signaling pathway, leading to transcriptional activation of ID3 (inhibitor of DNA binding 3) that promotes cell proliferation. In conclusion, ovarian cancer tissues secrete STIP1 into the local environment and eventually into blood circulation of patients. In an autocrine and/or paracrine fashion, secreted STIP1 stimulates cancer cell proliferation by binding to ALK2 and activating the SMAD-ID3 signaling pathways. Elucidation of the mechanism by which STIP1 stimulates cancer cell proliferation may pave the way for developing novel therapeutic strategies for treatment of ovarian cancer. SKOV3 cell,treated without rhSTIP1 SKOV3 cell,treated with rhSTIP1 SKOV3 cell,treated without rhSTIP1-2 SKOV3 cell,treated with rhSTIP1-2
2013-03-09 | E-GEOD-36383 | biostudies-arrayexpress
Project description:Stress-induced phosphoprotein 1 (STIP1), a co-chaperone that organizes other chaperones- heat shock proteins (HSP), was recently shown to be secreted by human ovarian cancer cells to induce cell proliferation. In neuronal tissues, binding to prion protein was required for STIP1 to activate the ERK (extracellular regulated MAP kinase) signaling pathways. However, in this study, we found that STIP1 stimulated cell proliferation of ovarian cancer via a bone morphogenetic protein (BMP) signaling pathway, not through the prion-ERK pathway. The STIP1 binding to a BMP receptor, ALK2 (activin A receptor, type II-like kinase 2), was necessary and sufficient to stimulate cancer cell proliferation. The binding of STIP1 to ALK2 activated the SMAD signaling pathway, leading to transcriptional activation of ID3 (inhibitor of DNA binding 3) that promotes cell proliferation. In conclusion, ovarian cancer tissues secrete STIP1 into the local environment and eventually into blood circulation of patients. In an autocrine and/or paracrine fashion, secreted STIP1 stimulates cancer cell proliferation by binding to ALK2 and activating the SMAD-ID3 signaling pathways. Elucidation of the mechanism by which STIP1 stimulates cancer cell proliferation may pave the way for developing novel therapeutic strategies for treatment of ovarian cancer.
2013-03-09 | GSE36383 | GEO
Project description:Stress-induced phosphoprotein 1 (STIP1) is a co-chaperone that regulates other chaperone proteins that was recently shown to be secreted by ovarian cancer cells to induce cell proliferation. In this study, we found that STIP1 induced the phosphorylation of endogenous SMAD1/5, and knockdown of SMAD1/4/5 blocked STIP1-activated ID3 expression. Inhibition of ALK2, a serine/threonine kinase receptor, with siRNA or the specific inhibitor LDN193189, blocked STIP1-induced phosphorylation of SMAD1/5 and inhibited STIP1-related cell proliferation. The signaling pathway was found to involve binding of secreted STIP1 to ALK2, phosphorylation of SMAD, and activation of ID3 to induce cell proliferation was identified not only by in vitro immunofluorescent microscopy and biochemical identification of complex formation, but also by in vivo immunohistochemical analyses of ovarian cancer tissues. MDAH2774 cell treated with rhSTIP1 MDAH2774 cell treated without rhSTIP1 MDAH2774 cell treated with rhSTIP1-2 MDAH2774 cell treated without rhSTIP1-2
2012-03-03 | E-GEOD-27654 | biostudies-arrayexpress
Project description:Stress-induced phosphoprotein 1 (STIP1) is a co-chaperone that regulates other chaperone proteins that was recently shown to be secreted by ovarian cancer cells to induce cell proliferation. In this study, we found that STIP1 induced the phosphorylation of endogenous SMAD1/5, and knockdown of SMAD1/4/5 blocked STIP1-activated ID3 expression. Inhibition of ALK2, a serine/threonine kinase receptor, with siRNA or the specific inhibitor LDN193189, blocked STIP1-induced phosphorylation of SMAD1/5 and inhibited STIP1-related cell proliferation. The signaling pathway was found to involve binding of secreted STIP1 to ALK2, phosphorylation of SMAD, and activation of ID3 to induce cell proliferation was identified not only by in vitro immunofluorescent microscopy and biochemical identification of complex formation, but also by in vivo immunohistochemical analyses of ovarian cancer tissues.
2012-03-03 | GSE27654 | GEO
Project description:Transforming growth factor-β (TGF-β) signaling stimulates cell movement and plasticity by inducing epithelial-to-mesenchymal transition (EMT). This process is aberrantly activated in cancer and facilitates tumor cell migration, invasion, metastasis, and therapy resistance. In this study, we identified the lncRNA eSNAI1 (SCREEM2) as a potent activator of TGF-β/SMAD signaling and SNAI1 expression. eSNAI1 depletion reduces TGF-β-induced EMT, migration, in vivo extravasation, stemness, and chemotherapy resistance of breast cancer cells. eSNAI1 promotes TGF-β/SMAD signaling by inhibiting TGF-β type I receptor polyubiquitination and proteasomal degradation. eSNAI1 stimulates the expression of the nearby gene SNAI1, which encodes the EMT transcription factor SNAI1 that facilitates TGF-β/SMAD signaling by retaining the inhibitory SMAD7 in the nucleus. Mechanistically, eSNAI1 acts as an enhancer RNA (eRNA) to potentiate SNAI1 expression through in-cis regulation. Furthermore, we uncovered that eSNAI1 interacts with and reinforces the binding of the co-activator bromodomain-containing protein 4 (BRD4) to the H3 lysine 27 acetylation (H3K27ac)-enriched SNAI1 enhancer region. Our findings identify eSNAI1 as a potent activator of TGF-β signaling and a promising therapeutic target to mitigate overactive TGF-β signaling and EMT in cancer cells.
2025-03-06 | GSE276203 | GEO
Project description:Studies have shown that leptin activates several signaling pathways and stimulates the expression of numerous downstream genes and that the key transcription factor that exerts this effect might serve as a promising therapeutic target in leptin-driven ovarian cancer. cJun is a widely recognized transcription factor that is located downstream of MAPK signaling pathways, and encodes a nuclear protein that regulates various aspects of cell growth and differentiation. c-Jun is activated by JNK through phosphorylation at Ser63, Ser73, Thr91, and Thr93, and by ERK and p38 via increased gene expression. However, whether c-Jun is involved in leptin-mediated stemness maintenance in ovarian cancer remains mostly unknown.
2025-10-01 | GSE277884 | GEO
Project description:Small extracellular vesicles secreted from senescent cells promote cancer cell proliferation through EphA2.
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Project description:Wnt/beta-catenin signaling is involved in various aspects of skeletal muscle development and regeneration. Using C2C12 cells, we examined intracellular signaling and gene transcription during myoblast proliferation and differentiation. The results of the present studies suggest that Wnt signaling is interacting with TGF-beta superfamily signaling through Smad activation. Single analysis for each condition (proliferating C2C12 cells, differentiating C2C12 cells, proliferating Wnt4-overexpressing C2C12 subline cells).
2013-06-21 | E-GEOD-40456 | biostudies-arrayexpress
Project description:ZKSCAN3 promotes ovarian cancer cell proliferation through upregulating HSPB1
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