Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA393435 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This study uncovers the cooperative and opposing effects of CD24 and RCC2 on tumor metastasis. CD24 regulates RCC2 through ubiquitination and degradation, and their interaction influences the β-catenin signaling pathway. RCC2 suppresses tumor metastasis by promoting cytoskeletal reorganization and degrading Vimentin, providing a deeper understanding of the molecular mechanisms underlying prostate cancer metastasis.
2025-07-23 | PXD056404 | Pride
Project description:CD24 plays a crucial role in tumor growth and metastasis, including in prostate cancer. While CD24 stimulates prostate cancer cell growth by controlling the ARF-NPM interaction and p53 inactivation, the mechanism of CD24-mediated metastasis remains elusive. This study identifies a direct interaction between CD24 and RCC2 with roles in prostate cancer cell proliferation and migration. Immunohistochemical analysis of primary prostate cancer samples showed expression of CD24 in 49% of samples and RCC2 in 82%, with a positive correlation between their protein levels. Their co-expression, particularly the binding of CD24 to the C-terminal domain of RCC2, supports their direct interaction, which may regulate cell motility and adhesion. Functional assays revealed that knockout (KO) of RCC2 in DU145 and PC3 prostate cancer cells inhibited cell proliferation but unexpectedly enhanced cell migration and invasion, while CD24 KO reduced proliferation and migration. Notably, dual KOs of CD24 and RCC2 led to a significant decrease in cell proliferation but showed mixed effects on migration, indicating a complex interplay between these proteins. In vivo, RCC2 KO in prostate cancer cells promoted spontaneous lung metastasis without significantly altering primary tumor growth, contrasting with CD24 KO, which reduced tumor growth and metastasis. Mechanistically, RCC2 was shown to ubiquitinate and degrade Vimentin, influencing cytoskeletal dynamics and migratory behavior. Furthermore, CD24 was found to ubiquitinate and degrade RCC2, leading to modulation of the β-catenin signaling pathway. RCC2 KO increased β-catenin activation and decreased the expression of its inhibitors AXIN2 and APC, while CD24 KO led to β-catenin inactivation. This opposing regulation of β-catenin signaling by CD24 and RCC2 underscores their differential roles in prostate cancer cell migration. These findings provide new insights into the molecular mechanisms underlying prostate cancer growth and metastasis and identify the CD24-RCC2 axis as a potential therapeutic target for controlling tumor growth and metastasis in prostate cancer.
2025-07-21 | GSE277962 | GEO
Project description:<p>The spread of cancer to bone is invariably fatal, with complex cross-talk between tumor cells and the bone microenvironment responsible for driving disease progression. By combining in silico analysis of patient datasets with metabolomic profiling of prostate cancer cells cultured with bone cells, we demonstrate the changing energy requirements of prostate cancer cells in the bone microenvironment, identifying the pentose phosphate pathway (PPP) as elevated in prostate cancer bone metastasis, with increased expression of the PPP rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD) associated with a reduction in progression-free survival. Genetic and pharmacologic manipulation demonstrates that G6PD inhibition reduces prostate cancer growth and migration, associated with changes in cellular redox state and increased chemosensitivity. Genetic blockade of G6PD in vivo results in reduction of tumor growth within bone. In summary, we demonstrate the metabolic plasticity of prostate cancer cells in the bone microenvironment, identifying the PPP and G6PD as metabolic targets for the treatment of prostate cancer bone metastasis.</p>
2024-08-19 | MTBLS3973 | MetaboLights
Project description:The propensity for prostate cancer to metastasize to bone led us and others to propose that bidirectional interaction between prostate cancer cells and bone are critical for the preferential metastasis of PCa to bone. We previous identified a secreted isoform of ErbB3 (p45-sErbB3) from the bone marrow supernatants of patients with prostate cancer and bone metastasis. Immunohistochemical analysis of p45-sErbB3 expression in human specimens showed that p45-sErbB3 was highly expressed in metastatic prostate cancer cells in bone. Here we show that p45-sErbB3 stimulates calvarial bone to secrete factors that increase the invasiveness of prostate cancer cells in Boyden chamber invasion assay. We used gene array analysis to identify p45-sErbB3 regulated osteoblast genes that may enhance the invasiveness of PC-3 cells and found that p45-sErbB3 stimulated the expression of osteonectin, biglycan, and type I collagen in mouse calvaria. We further showed that recombinant osteonectin increases the invasiveness of PC-3 cells and osteonectin neutralizing antibody blocked p45-sErbB3 mediated invasiveness. These results suggest that p45-sErbB3 enhances the invasiveness of PC-3 cells is due, at least in part, to the stimulation of the secretion of osteonectin from bone. Thus, p45-sErbB3 mediates the bi-directional interaction between PCa cells and bone through osteonectin. Sample 1: non-treated calvaria RNA, Group 1 Sample 2: sErbB3 (100ng/ml) treated calvaria RNA, Group 2 Array: GE-supper array MM026 (total 96 genes, with 10 housekeeping genes) (service from SuperArray Bioscience Corporation: http://www.superarray.com
2008-05-01 | E-GEOD-8001 | biostudies-arrayexpress
Project description:The propensity for prostate cancer to metastasize to bone led us and others to propose that bidirectional interaction between prostate cancer cells and bone are critical for the preferential metastasis of PCa to bone. We previous identified a secreted isoform of ErbB3 (p45-sErbB3) from the bone marrow supernatants of patients with prostate cancer and bone metastasis. Immunohistochemical analysis of p45-sErbB3 expression in human specimens showed that p45-sErbB3 was highly expressed in metastatic prostate cancer cells in bone. Here we show that p45-sErbB3 stimulates calvarial bone to secrete factors that increase the invasiveness of prostate cancer cells in Boyden chamber invasion assay. We used gene array analysis to identify p45-sErbB3 regulated osteoblast genes that may enhance the invasiveness of PC-3 cells and found that p45-sErbB3 stimulated the expression of osteonectin, biglycan, and type I collagen in mouse calvaria. We further showed that recombinant osteonectin increases the invasiveness of PC-3 cells and osteonectin neutralizing antibody blocked p45-sErbB3 mediated invasiveness. These results suggest that p45-sErbB3 enhances the invasiveness of PC-3 cells is due, at least in part, to the stimulation of the secretion of osteonectin from bone. Thus, p45-sErbB3 mediates the bi-directional interaction between PCa cells and bone through osteonectin. Keywords: Prostate cancer, bone metastasis, P45-sErbB3, osteonectin
2008-05-01 | GSE8001 | GEO
Project description:Most cancer deaths are due to metastatic dissemination to distant organs. Bone is the most frequently affected organ in metastatic prostate cancer and a major cause of prostate cancer deaths. Yet, our partial understanding of the molecular factors that drive bone metastasis has been a limiting factor for developing preventative and therapeutic strategies to improve patient survival and well-being. Although recent studies have uncovered molecular alterations that occur in prostate cancer metastasis, their functional relevance for bone metastasis is not well understood. Using genome-wide CRISPR activation and inhibition screens we have identified multiple drivers and suppressors of prostate cancer metastasis. Through functional validation, including innovative organ-on-a-chip invasion platform for studying bone tropism, our study identifies the transcriptional modulator, CITED2, as a novel driver of prostate cancer bone metastasis and uncovers multiple new potential molecular targets for bone metastatic disease.
2024-02-22 | GSE253815 | GEO
Project description:To understand whether CD24, a potential marker for ovarian cancer stem cells,-dependent microRNA expression affects ovarian cancer stemness, microRNA expression was compared between CD24-negative and CD24-positive ovarian cancer cells.
2023-12-01 | GSE164748 | GEO
Project description:Clinically, osteolytic phenotype is rare in prostate cancer. The molecular mechanism of bone metastasis in PCa is not fully understood. We performed RNA-seq to identify osteogenic and tumor associated roles in prostate cancer by a co-culture of osteoblasts (MG63) and prostate cancer cells (C4-2, C4-2B, 22Rv1 and DU145). We compared osteoblastic prostate cancer with osteolytic prostate cancer to evaluate the difference in phenotype of bone metastasis.
2023-09-26 | GSE210729 | GEO
Project description:Prostate cancer is the leading type of cancer diagnosed and the third leading cause of cancer-related deaths worldwide each year in men. The limitations of the current prostate cancer screening test demands new biomarkers for early diagnosis of prostate cancer metastasis to bone. In this study, we performed a deep proteomic analysis of secreted proteins from the prostate cancer bone metastasis cell line, PC-3, and normal prostate cell line, RWPE-1. Here, we quantified 917 proteins and found 68 highly secreted in PC-3 versus RWPE-1 cells using LC-MS/MS. To characterize the highly secreted proteins in the PC-3 cell line to identify biomarker proteins, the quantifiable proteins were divided into four quantitative categories (Q1-Q4). The KEGG pathways of lysine degradation and osteoclast differentiation were enriched in Q4, the highly secreted group. Transforming growth factor (TGF) beta family proteins related to osteoclast differentiation were identified as key regulators in PC-3 cells. Among the 68 highly secreted proteins, pentraxin, follistatin, and TGF-beta family members were confirmed by immunoblots. In particular, serpin B3, modulated by TGF-beta, was detected and its selective expression and secretion in PC-3 cells was confirmed. In the present study, we suggest that serpin B3 is a novel biomarker candidate for diagnosis of prostate cancer metastasis to the bone.
2017-08-30 | PXD006252 | Pride
Project description:KRAS mutations are a predominant driver of metastatic colorectal cancer (mCRC), with approximately 10% of patients harboring the KRAS p.G12C variant. Despite the development of KRASG12C (G12Ci) and EGFR (EGFRi) inhibitors such as sotorasib and panitumumab, therapeutic resistance remains a major limitation. To define resistance mechanisms, we analyzed tissue biopsies from patients treated with G12Ci+EGFRi and employed Xenium spatial transcriptomics (Xenium ST), along with comprehensive multi-omics profiling of patient-derived xenograft (PDX) models. Known genomic alterations including NRAS p. Q61K mutations and KRASG12C amplifications were observed; however, non-genomic resistance was strongly associated with activation of the YAP-TEAD pathway. Xenium ST data revealed two key tumor subpopulations: tumor intestinal stem cells (TISCs), marked by upregulation of KRAS and YAP, and neuroendocrine-like (NE) cells, which showed KRAS upregulation alone. G12Ci+EGFRi-resistant PDX models were enriched for TISCs and associated stemness programs. The addition of a TEAD inhibitor (TEADi; IAG-933) to dual therapy induced deep tumor regression and suppressed KRAS, YAP, stemness pathways; however, NE-like cells were enriched following triple therapy. These findings suggest that TEADi enhances the efficacy of KRASG12C + EGFR inhibition by targeting TISCs but may not eliminate NE-like subpopulations, which could mediate TEAD-independent resistance and represent a therapeutic challenge.
2025-09-24 | GSE308699 | GEO