Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA170987 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Bone is the primary site of breast cancer metastasis and complications associated with bone metastases can lead to a significantly decreased quality of life in these patients. Thus, it is essential to gain a better understanding of the molecular mechanisms that underlie the emergence and growth of breast cancer skeletal metastases. Methods: To search for novel molecular mediators that influence breast cancer bone metastasis, we generated gene expression profiles from laser capture micro-dissected trephine biopsies of both breast cancer bone metastases and primary breast tumors that metastasized to bone. Bioinformatics analysis identified genes that are differentially expressed in breast cancer bone metastases compared to primary mammary tumors. Results: ABCC5, an ATP-dependent transporter, was found to be overexpressed in breast cancer osseous metastases relative to primary mammary tumors. In addition, ABCC5 was significantly up-regulated in human and mouse breast cancer cell lines with high bone-metastatic potential. Stable knockdown of ABCC5 significant reduced bone metastatic burden and osteolytic bone destruction in mice. The decrease in osteolysis was further associated with diminished osteoclast numbers. Conclusions: Our data, for the first time, suggests that ABCC5 functions as a mediator of breast cancer skeletal metastasis. ABCC5 expression in breast cancer cells is important for the efficient bone resorption mediated by osteoclasts. Hence, ABCC5 may be a potential therapeutic target for breast cancer bone metastasis. primary breast tumors vs. bone trephine biopsies
2012-11-09 | E-GEOD-39494 | biostudies-arrayexpress
Project description:<p>Bone metastasis is a lethal consequence of breast cancer. AT-rich interaction domain 1A gene (ARID1A), a subunit of the switch/sucrose non-fermentable (SWI/SNF) complex, regulates immunosuppressive tumor microenvironment. ARID1A deficient triple negative breast cancer promotes bone metastasis.To further explore the mechanisms underlying ARID1A deficiency-induced bone metastasis, we performed integrated metabolomic and transcriptome analyses on ARID1A-NC and ARID1A-KO cells.</p>
2026-03-24 | MTBLS12768 | MetaboLights
Project description:Bone metastasis remains a major cause of morbidity in ER+ breast cancer, with RANKL inhibitor resistance emerging as a critical clinical challenge. Nearly 40% of patients develop progressive skeletal lesions despite denosumab therapy, highlighting an urgent need to identify resistance mechanisms and alternative therapeutic strategies. We identified a RANKL-independent osteoclast activation pathway mediated by the CRKL/circCCDC50/NFATc1 axis. Mechanistically, CRKL promotes EIF4A3-dependent circCCDC50 biogenesis, which is packaged into large oncosomes and transferred to osteoclast precursors. Nuclear circCCDC50 recruits CARM1 to epigenetically activate NFATc1 transcription, establishing a self-reinforcing loop that sustains osteolysis despite RANKL blockade. Pharmacological inhibition of CARM1 (TP-064) effectively suppresses osteoclastogenesis and bone metastasis in denosumab-resistant models. These findings reveal a targetable resistance mechanism and provide a clinically actionable strategy to overcome microenvironment-driven metastasis through dual targeting of tumor and bone niches.
2026-03-16 | GSE317129 | GEO
Project description:Bone metastasis remains a major cause of morbidity in ER+ breast cancer, with RANKL inhibitor resistance emerging as a critical clinical challenge. Nearly 40% of patients develop progressive skeletal lesions despite denosumab therapy, highlighting an urgent need to identify resistance mechanisms and alternative therapeutic strategies. We identified a RANKL-independent osteoclast activation pathway mediated by the CRKL/circCCDC50/NFATc1 axis. Mechanistically, CRKL promotes EIF4A3-dependent circCCDC50 biogenesis, which is packaged into large oncosomes and transferred to osteoclast precursors. Nuclear circCCDC50 recruits CARM1 to epigenetically activate NFATc1 transcription, establishing a self-reinforcing loop that sustains osteolysis despite RANKL blockade. Pharmacological inhibition of CARM1 (TP-064) effectively suppresses osteoclastogenesis and bone metastasis in denosumab-resistant models. These findings reveal a targetable resistance mechanism and provide a clinically actionable strategy to overcome microenvironment-driven metastasis through dual targeting of tumor and bone niches.
2026-03-16 | GSE317130 | GEO
Project description:Bone is the primary site of breast cancer metastasis and complications associated with bone metastases can lead to a significantly decreased quality of life in these patients. Thus, it is essential to gain a better understanding of the molecular mechanisms that underlie the emergence and growth of breast cancer skeletal metastases. Methods: To search for novel molecular mediators that influence breast cancer bone metastasis, we generated gene expression profiles from laser capture micro-dissected trephine biopsies of both breast cancer bone metastases and primary breast tumors that metastasized to bone. Bioinformatics analysis identified genes that are differentially expressed in breast cancer bone metastases compared to primary mammary tumors. Results: ABCC5, an ATP-dependent transporter, was found to be overexpressed in breast cancer osseous metastases relative to primary mammary tumors. In addition, ABCC5 was significantly up-regulated in human and mouse breast cancer cell lines with high bone-metastatic potential. Stable knockdown of ABCC5 significant reduced bone metastatic burden and osteolytic bone destruction in mice. The decrease in osteolysis was further associated with diminished osteoclast numbers. Conclusions: Our data, for the first time, suggests that ABCC5 functions as a mediator of breast cancer skeletal metastasis. ABCC5 expression in breast cancer cells is important for the efficient bone resorption mediated by osteoclasts. Hence, ABCC5 may be a potential therapeutic target for breast cancer bone metastasis.
2012-11-09 | GSE39494 | GEO
Project description:Bone-marrow-derived mesenchymal stem cells promote breast cancer metastasis
| PRJNA102435 | ENA
Project description:Programmed death-ligand 1 (PD-L1) is predominantly expressed in the antigen-presenting cells (APCs) that are originated and abundant in bone marrow. The roles of PD-L1 in bone cell differentiation and cancer bone metastasis remain unclear. Here we show that PD-L1 antibody or PD-L1 conditional knockout in the hematopoietic or myeloid lineage suppresses osteoclast differentiation in vitro and in vivo. Bone metastases of breast cancer and melanoma are diminished by PD-L1 antibody or PD-L1 deletion in the myeloid lineage. Transcriptional profiling of bone marrow cells reveals that PD-L1 deletion in the myeloid cells up-regulates immune stimulatory genes, leading to increased macrophage M1 polarization, decreased M2 polarization, enhanced IFN? signaling, and elevated T cell recruitment and activation. All these alterations result in heightened anti-tumor immunity in the cancer microenvironment. Our findings support PD-L1 antibody as a potent therapy for bone metastasis of breast cancer and melanoma by simultaneously suppressing osteoclast and enhancing immunity.
2022-03-07 | GSE190715 | GEO
Project description:Bone metastasis remains a major cause of morbidity in ER+ breast cancer, with RANKL inhibitor resistance emerging as a critical clinical challenge. Nearly 40% of patients develop progressive skeletal lesions despite denosumab therapy, highlighting an urgent need to identify resistance mechanisms and alternative therapeutic strategies. We identified a RANKL-independent osteoclast activation pathway mediated by the CRKL/circCCDC50/NFATc1 axis. Mechanistically, CRKL promotes EIF4A3-dependent circCCDC50 biogenesis, which is packaged into large oncosomes and transferred to osteoclast precursors. Nuclear circCCDC50 recruits CARM1 to epigenetically activate NFATc1 transcription, establishing a self-reinforcing loop that sustains osteolysis despite RANKL blockade. Pharmacological inhibition of CARM1 (TP-064) effectively suppresses osteoclastogenesis and bone metastasis in denosumab-resistant models. These findings reveal a targetable resistance mechanism and provide a clinically actionable strategy to overcome microenvironment-driven metastasis through dual targeting of tumor and bone niches.
2026-01-29 | PXD073739 |
Project description:The IKKβ/FoxO3a axis regulates breast cancer tumorigenesis and bone metastasis
| PRJNA291216 | ENA