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HGSC metastasis requires tumor cells to evade anoikis during detachment from the fallopian tube epithelium. Through integrative analysis of hyaluronic acid (HA) metabolism-associated genes in transcriptomic datasets, calcineurin homologous protein 1 (CHP1) was identified as a novel mediator of HGSC metastasis. Mechanistically, CHP1 ablation disrupted spheroid morphogenesis in 3D models, inducing aberrant multi-spheroid formation and reduced structural integrity, with impaired cell extrusion from mosaic spheroids. Bioinformatic and experimental validation revealed that CHP1 interacted with the mechanosensitive channel transmembrane protein 87A (TMEM87A), forming a putative mechanosensing complex that may regulate metastasis via the YAP\u2013GPC6\u2013WNT5A\/Hedgehog signaling axis; knockout of either gene downregulated\n                    <jats:italic>WNT5A\/GPC6<\/jats:italic>\n                    and inhibited WNT5A\/Hedgehog pathways. In vivo,\n                    <jats:italic>CHP1<\/jats:italic>\n                    or\n                    <jats:italic>TMEM87A<\/jats:italic>\n                    knockout significantly suppressed orthotopic tumor growth and metastasis in NSG mice, indicating a role in overall tumor progression beyond metastasis alone. Drug repurposing identified sodium gluconate (a TMEM87A modulator) as a therapeutic candidate: low-dose treatment (1\u00a0mg\/kg, weekly) significantly reduced tumor burden by disrupting CHP1-TMEM87A binding and inhibiting downstream Hedgehog\/PTCH1 signaling, as the cellular thermal shift assay (CETSA), microscale thermophoresis (MST), surface plasmon resonance (SPR), and co-immunoprecipitation. Clinically, high\n                    <jats:italic>CHP1\/TMEM87A<\/jats:italic>\n                    expression exhibited stage-dependent prognostic significance (favorable in early-stage, unfavorable in late-stage HGSC), as assessed by Kaplan\u2013Meier survival analysis of publicly available datasets. These findings suggest that the CHP1-TMEM87A complex may serve as a mechanosensitive regulator of HGSC metastasis and propose gluconate-based targeting as a promising therapeutic strategy.\n                  <\/jats:p>","DOI":"10.1186\/s43556-026-00487-4","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T09:18:01Z","timestamp":1780910281000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting the Calcineurin Homologous Protein 1 (CHP1)-Transmembrane Protein 87A (TMEM87A) mechanosensing complex: a druggable vulnerability in metastatic ovarian cancer"],"prefix":"10.1186","volume":"7","author":[{"given":"Ming-Zhu","family":"Jin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng-An","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Di","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"issue":"1","key":"487_CR1","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3322\/caac.21871","volume":"75","author":"RL Siegel","year":"2025","unstructured":"Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. 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