New ProteomeXchange dataset PXD073739

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Dear ProteomeXchange subscriber, a new ProteomeXchange dataset is being announced. To see more information, click here:

https://proteomecentral.proteomexchange.org/dataset/PXD073739

Summary of dataset

Status: new
Identifier: PXD073739
HostingRepository: iProX
Species: Homo sapiens
Title: Targeting RANKL-Independent Osteoclastogenesis Overcomes Denosumab Resistance in ER+ Breast Cancer Bone Metastasis
Submitter: Jinpeng Luo
LabHead: Chang Gong
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.

HTML_URL: https://proteomecentral.proteomexchange.org/dataset/PXD073739
XML_URL: https://proteomecentral.proteomexchange.org/dataset/PXD073739&outputMode=XML