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Unraveling the regulators behind lung cancer growth and its metastatic spread, along with understanding the underlying mechanisms, is crucial for developing novel and effective therapeutic strategies. While much research has focused on identifying potential oncogenes or tumor suppressors, the roles of certain genes can vary depending on the context and may even exhibit contradictory effects. In this study, we demonstrate that acyl-CoA binding domain containing 3 (ACBD3), a Golgi resident protein, promotes primary lung cancer growth by recruiting phosphatidylinositol (PI)-4-kinase III\u03b2 (PI4KB) to the Golgi, thereby enhancing oncogenic secretion in chromosome 1q-amplified lung cancer cells. Conversely, in chromosome 1q-diploid lung cancer cells, ACBD3 acts as a suppressor of lung cancer metastasis by inhibiting the NOTCH signaling pathway and reducing cancer cell motility. This highlights the intricacy of cancer progression and cautions against simplistic approaches targeting individual oncogenes for cancer therapy.<\/jats:p>","DOI":"10.1038\/s41388-025-03360-w","type":"journal-article","created":{"date-parts":[[2025,4,6]],"date-time":"2025-04-06T08:54:32Z","timestamp":1743929672000},"page":"2078-2090","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dichotomous roles of ACBD3 in NSCLC growth and metastasis"],"prefix":"10.1038","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8603-5700","authenticated-orcid":false,"given":"Xiaochao","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyam","family":"Banerjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shike","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derrick L.","family":"Cardin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6090-703X","authenticated-orcid":false,"given":"Chad J.","family":"Creighton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William K.","family":"Russell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,6]]},"reference":[{"key":"3360_CR1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3322\/caac.21763","volume":"73","author":"RL Siegel","year":"2023","unstructured":"Siegel RL, Miller KD, Wagle NS, Jemal A. 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