Loss-of-function of IFT88 determines metabolic phenotypes in thyroid cancer

Abstract

Primary cilia are microtubule-based, dynamic organelles characterized by continuous assembly and disassembly. The intraflagellar transport (IFT) machinery, including IFT88 in cilia, is involved in the maintenance of bidirectional motility along the axonemes, which is required for ciliogenesis and functional competence. Cancer cells are frequently associated with loss of primary cilia and IFT functions. However, there is little information on the role of IFT88 or primary cilia in the metabolic remodeling of cancer cells. Therefore, we investigated the cellular and metabolic effects of the loss-of-function (LOF) mutations of IFT88/primary cilia in thyroid cancer cells. IFT88-deficient 8505C thyroid cancer cells were generated using the CRISPR/Cas9 system, and RNA-sequencing analysis was performed. LOF of the IFT88 gene resulted in a marked defect in ciliogenesis and mitochondrial oxidative function. Gene expression patterns in IFT88-deficient thyroid cancer cells favored glycolysis and lipid biosynthesis. However, LOF of IFT88/primary cilia did not promote thyroid cancer cell proliferation, migration, and invasion. The results suggest that IFT88/primary cilia play a role in metabolic reprogramming in thyroid cancer cells.

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Acknowledgements

This work was supported by a grant (NRF-2015R1C1A1A02037434) from NRF/MISIT, Korea and a grant from the Catholic Medical Center Research Foundation made in the program year of 2016, and a grant from Daejeon St. Mary’s Hospital. M.S. was supported by a grant from the NRF funded by the Ministry of Science and ICT (grant number: NRF-2014M3A9D8034464) and a grant from the NRF/MISIT of Korea (grant number: NRF-2015M3A9B3028218).

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Correspondence to Minho Shong.

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Lee, J., Yi, S., Won, M. et al. Loss-of-function of IFT88 determines metabolic phenotypes in thyroid cancer. Oncogene 37, 4455–4474 (2018). https://doi.org/10.1038/s41388-018-0211-6

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