COPZ1 depletion induces cell death through different mechanisms in <i>in vitro</i> murine models of thyroid cancer

OBJECTIVE: In last years the discovery of non-oncogene addiction (NOA) has expanded the cancer targets repertoire. Specifically, novel strategies are aimed to counteract the dependency of cancer cells on normal genes that are essential to sustain their stress phenotype. Among NOA genes, discovered by our group, that are essential for human thyroid cancer cells, we extensively focused on COPZ1, a subunit of coatomer complex I. We previously reported that in in vitro human thyroid cancer models, COPZ1 depletion can induce IFN-I mediated stimulatory effects, which culminates in immunogenic cell death. To evaluate in vivo the effects of COPZ1 depletion on immunity and inflammation, generation of syngeneic mouse models are needed. Towards this aim, in this work we studied in vitro the dependency on COPZ1 in murine thyroid cancer cell lines. METHODS: Cell viability was assessed through crystal violet assay and commercially available kit. qRT-PCR and western blot were used to evaluate the expression of genes and protein of interest; commercially available kits were used for monitoring cytokines release and oxidative status. RESULTS: Analogously to the human counterpart, COPZ1 silencing impaired cell proliferation and induced ER stress in four cell lines. The transcription and secretory IFN-I related program was activated in two of four cell lines. In the other two cell lines we detected increase of ROS production, lipid peroxidation and Ca2+ level. CONCLUSION: Activation of inflammatory effects after COPZ1 silencing, is cell line dependent.