{"doi":"10.1126/scitranslmed.aax3772","title":"PI4KIIIβ is a therapeutic target in chromosome 1q–amplified lung adenocarcinoma","abstract":"Heightened secretion of protumorigenic effector proteins is a feature of malignant cells. Yet, the molecular underpinnings and therapeutic implications of this feature remain unclear. Here, we identify a chromosome 1q region that is frequently amplified in diverse cancer types and encodes multiple regulators of secretory vesicle biogenesis and trafficking, including the Golgi-dedicated enzyme phosphatidylinositol (PI)-4-kinase IIIβ (PI4KIIIβ). Molecular, biochemical, and cell biological studies show that PI4KIIIβ-derived PI-4-phosphate (PI4P) synthesis enhances secretion and accelerates lung adenocarcinoma progression by activating Golgi phosphoprotein 3 (GOLPH3)-dependent vesicular release from the Golgi. PI4KIIIβ-dependent secreted factors maintain 1q-amplified cancer cell survival and influence prometastatic processes in the tumor microenvironment. Disruption of this functional circuitry in 1q-amplified cancer cells with selective PI4KIIIβ antagonists induces apoptosis and suppresses tumor growth and metastasis. These results support a model in which chromosome 1q amplifications create a dependency on PI4KIIIβ-dependent secretion for cancer cell survival and tumor progression.","journal":"Science Translational Medicine","year":2020,"id":59159,"datarank":0.635115975689589,"base_score":4.23410650459726,"endowment":4.23410650459726,"self_citation_contribution":0.635115975689589,"citation_network_contribution":0.0,"self_endowment_contribution":0.635115975689589,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":68,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":311136,"name":"Priyam Banerjee","orcid":"0000-0001-9398-9345","position":1,"is_corresponding":false},{"id":235781,"name":"Edward A. 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