Dysregulated Golgi homeostasis has emerged as a potential contributor to tumor development and progression by altering the surface and secreted proteome, as well as Golgi-specific modifications. In this proposal we aim to uncover the effects of Golgi stress and perturbed Golgi morphology on cancer cell behavior and their interactions with the immune cells. Our research objectives encompass three specific aims: First, characterizing Golgi stress-induced Golgi fragmentation in a diverse panel of cancer cell lines, shedding light on the mechanisms underlying this phenomenon. Second, investigating the influence of Golgi stress on the surface and secreted proteomes of cancer cells, identifying pivotal effector proteins involved in mediating these alterations. Third, evaluating whether and how Golgi-related aberrations can disrupt interactions between cancer cells and immune cells in in vitro settings, offering insights into the intricate dynamics of tumor-immune crosstalk. Altogether, this comprehensive investigation into the role of Golgi stress in shaping cancer cell phenotype, proteome composition, and immune interactions promises to provide novel insights into tumor-host relationships and may uncover novel therapeutic strategies that harness the Golgi apparatus as a potential target to improve cancer immunotherapy outcomes.
