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Intratumoral DTP cells can herald a worse clinical outcome, but the way in which DTP cells influence LUAD progression remains unclear. Osi-resistant (OR) cells exhibit typical DTP cell features, including a propensity to undergo senescence and epithelial-mesenchymal transition (EMT), which can activate heightened secretory states. Therefore, we postulated that OR cells influence LUAD progression through paracrine mechanisms. To test this hypothesis, we utilized congenic pairs of EGFR-mutant LUAD cell lines in which drug-naive (DN) cells were rendered OR by chronic exposure to escalating doses of Osi. Cocultured in vitro or coinjected into mice, paracrine signals from OR cells enhanced the growth and metastatic properties of DN cells. EMT and senescence activated nonoverlapping secretomes, and OR cells governed DN cells by undergoing EMT but not senescence. Mechanistically, Osi rapidly increased TGF-\u03b22 levels to initiate EMT, which triggered a Golgi remodeling process that accelerated the biogenesis and anterograde trafficking of secretory vesicles. The protumorigenic activity of OR cells was diminished by depletion of EMT-dependent secreted proteins or the EMT-activating transcription factor ZEB1. 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