Abstract 769: Zeb-1 contributes to the development of chemotherapeutic resistance in mantle cell lymphoma

Abstract

Abstract Despite progress overall in improving cancer treatments, the complete response of mantle cell lymphoma (MCL) is still limited due to the inevitable development of drug resistance. Understanding how MCL cells acquire resistance at the molecular level may be a key innovation to targeted therapy. We established a series of bortezomib (BTZ)-resistant MCL cells and performed gene/protein profiling along with metabolic fingerprinting using synchrotron-based Fourier-transform infrared spectroscopy. Zeb-1, an epithelial-mesenchymal transition-inducing transcription factor better known for promoting metastasis in solid carcinomas, was found to be aberrantly expressed in the resistant MCL cells in accordance with an excessive production of lipids. Ectopic expression of Zeb-1 in parental MCL cells rendered the cells to acquire apoptosis resistance to BTZ. Here we demonstrated, for the first time, two possible encompassing mechanisms for Zeb-1-mediated BTZ resistance: (i) Zeb-1 induces cancer stem cells, as evaluated by tumor spheres and aldehyde dehydrogenase activity; and (ii) Zeb-1 induces lipid reprograming that may interfere with cell growth and drug response. Together, our results unveil a novel role of Zeb-1 in MCL aggressiveness. These findings have a clinical significance insight to the development of chemotherapeutic resistance of MCL. Citation Format: Sudjit Luanpitpong, Jirarat Poohadsuan, Montira Janan, Kanjana Thumanu, Yon Rojanasakul, Surapol Issaragrisil. Zeb-1 contributes to the development of chemotherapeutic resistance in mantle cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 769.