6533b7dafe1ef96bd126eb94
RESEARCH PRODUCT
Targeting COPZ1 non-oncogene addiction counteracts the viability of thyroid tumor cells
Maria Chiara AnaniaSonia PagliardiniAngela GrecoGiuseppe Di MauroClaudio TripodoDaniele LecisLoredana ClerisGiacomo ManentiBeatrice BelmonteKatia TodoertiTiziana Di MarcoElena CettiAntonino NeriAntonino NeriAlessandro Gulinosubject
0301 basic medicineCancer ResearchTime FactorsCOPZ1ApoptosisCOPZ1Thyroid cancerThyroid NeoplasmThyroidRNAi TherapeuticCell death; COPZ1; Non-oncogene addiction; Thyroid carcinoma; Animals; Apoptosis; Autophagy; Cell Line Tumor; Cell Survival; Coatomer Protein; Endoplasmic Reticulum Stress; Female; Gene Expression Regulation Neoplastic; Humans; Mice Nude; RNA Interference; Signal Transduction; Thyroid Neoplasms; Time Factors; Transfection; Tumor Burden; Unfolded Protein Response; Xenograft Model Antitumor Assays; RNAi Therapeutics; Oncology; Cancer ResearchEndoplasmic Reticulum StressOncogene AddictionTumor BurdenGene Expression Regulation Neoplasticmedicine.anatomical_structureOncologyFemaleRNA InterferenceNon-oncogene addictionHumanSignal TransductionCell deathProgrammed cell deathXenograft Model Antitumor AssayTime FactorCell SurvivalMice NudeBiologyTransfectionCoatomer ProteinThyroid carcinomaThyroid carcinoma03 medical and health sciencesCell Line TumorAutophagymedicineAnimalsHumansThyroid NeoplasmsEndoplasmic Reticulum StreAnimalAutophagyApoptosimedicine.diseaseXenograft Model Antitumor AssaysRNAi Therapeutics030104 developmental biologyImmunologyUnfolded Protein ResponseCancer researchUnfolded protein responsedescription
Abstract Thyroid carcinoma is generally associated with good prognosis, but no effective treatments are currently available for aggressive forms not cured by standard therapy. To find novel therapeutic targets for this tumor type, we had previously performed a siRNA-based functional screening to identify genes essential for sustaining the oncogenic phenotype of thyroid tumor cells, but not required to the same extent for the viability of normal cells (non-oncogene addiction paradigm). Among those, we found the coatomer protein complex ζ1 (COPZ1) gene, which is involved in intracellular traffic, autophagy and lipid homeostasis. In this paper, we investigated the mechanisms through which COPZ1 depletion leads to thyroid tumor cell death. We showed that siRNA-mediated COPZ1 depletion causes abortive autophagy, endoplasmic reticulum stress, unfolded protein response and apoptosis. Interestingly, we observed that mouse tumor xenografts, locally treated with siRNA targeting COPZ1, showed a significant reduction of tumor growth. On the whole, we demonstrated for the first time the crucial role of COPZ1 in the viability of thyroid tumor cells, suggesting that it may be considered an attractive target for novel therapeutic approaches for thyroid cancer.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-01-01 |