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Although disrupting tumor-bone microenvironment crosstalk is a promising strategy, clinically actionable targets remain limited. Here, by analyzing bulk RNA sequencing data from bone metastatic tumors across multiple cancer types, we identified\n                    <jats:italic>PARP10<\/jats:italic>\n                    as a gene consistently upregulated in bone metastases. High\n                    <jats:italic>PARP10<\/jats:italic>\n                    expression in primary tumors was correlated with poor patient survival. Functional studies demonstrated that PARP10 promoted lung cancer growth and bone metastasis both in vitro and in vivo. Mechanistically, multi-omics integrated analyses revealed that\n                    <jats:italic>PARP10<\/jats:italic>\n                    deletion induced DNA damage and oxidative stress, and upregulated BCAT2 expression in a MYC-dependent manner to enhance BCAA catabolism. This metabolism exerts an adaptive compensatory effect on tumor cells via boosting mitochondrial oxidative phosphorylation, yet depletes bone microenvironmental BCAA and consequently suppresses osteoclast differentiation, thereby inhibiting bone metastasis. Importantly, pharmacological inhibition of PARP10 with OUL232 mitigated bone metastatic burden in mice without observable toxicity, demonstrating its therapeutic potential by concurrently inducing tumor cell apoptosis and disrupting the pro-metastatic niche. Our findings establish PARP10 as a central regulator of a targetable metabolic competition axis and propose its inhibition as a dual-mechanism strategy that simultaneously attacks tumor cells and disrupts the pro-metastatic niche.\n                  <\/jats:p>","DOI":"10.1038\/s41419-026-08989-3","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T21:56:21Z","timestamp":1781906181000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting the PARP10-BCAT2 axis disrupts branched-chain amino-acid metabolism to suppress bone metastasis in lung cancer"],"prefix":"10.1038","volume":"17","author":[{"given":"Yahan","family":"Qin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujian","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Chai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxia","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"8989_CR1","first-page":"229","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. 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