Stress-induced proteome remodeling at the Golgi-endosome interface.

Cellular stress response pathways support cell survival under stress and are often leveraged by cancer cells to gain advantageous traits. How cells respond to Golgi stress is incompletely understood, limiting insights into the role of Golgi stress in cancer. Here, we combined small-molecule stress models and proteomic analyses to elucidate stress-induced changes at the Golgi. Our data establish the depletion of Golgi transport proteins as a common response to different Golgi stressors, including ionophores and oxysterol-binding protein (OSBP) inhibitors. Ionophores further induce de novo expression of the stress response protein FAM129A (also known as NIBAN1), which localizes to the remodeled secretory pathway. In a group of melanoma cells, displaying a dedifferentiated epithelial-to-mesenchymal-transition (EMT)-like phenotype, FAM129A is constitutively expressed. In these cells, stress-induced localization of FAM129A to the secretory pathway is achieved by relocalization from the plasma membrane. Collectively, our data highlight the Golgi-endosome interface as a critical hub of the cellular response to Golgi stress and reveal cancer cell-specific effects of this response.