Yellow fluorescent protein (YFP) as a biosensor for intracellular iodide in thyroid cancer cells

Martin Read, Katie Baker, Caitlin Thornton, Mohammed Alshahrani, Alice Fletcher, Rebecca Thompson, Peter Haggie, Alan Verkman, Kristien Boelaert, Vicki Smith, Christopher McCabe

Research output: Contribution to conference (unpublished)Abstractpeer-review


New drug strategies are urgently needed to improve radioiodine uptake and efficiently ablate thyroid cancer cells thereby minimising the risk of recurrent disease. High-throughput screening (HTS) offers a promising approach to identify new candidate drugs that induce sodium iodide symporter (NIS) function to promote iodide uptake. However, significant progress has been limited by a lack of thyroid cell-based assays amenable to HTS.

Here, we investigated a thyroid cancer cell reporter consisting of a modified version of the yellow fluorescent protein (YFP-H148Q/I152L/F46L) as a biosensor of intracellular iodide. Iodide uptake was monitored by quenching of YFP-H148Q/I152L/F46L fluorescence using a HTS reader PHERAstar FSX.

We generated a panel of human thyroid cancer cell lines with stable overexpression of YFP-H148Q/I152L/F46L either alone or together with NIS. Importantly, the YFP cell-based assay was sensitive towards iodide uptake and robust with a Z’ value of 0.82 (e.g. maximal 12% YFP reduction at 8mM dose versus 40% YFP reduction at 68mM dose after 10 minutes). Kinetic measurements demonstrated that iodide uptake was rapid within 2 minutes with maximal quenching at 5-10 minutes depending on thyroid cancer cell type. Further, we validated the assay with a panel of reference compounds, which showed that the Src inhibitor PP1 was the most potent in enhancing iodide uptake, followed by selumetinib and SAHA.

In summary, we have developed a robust thyroid cell reporter assay that is amenable for HTS. Enhancement of iodide uptake is currently being evaluated utilizing this assay and a library of ~5300 well-annotated drugs.

Original languageEnglish
Publication statusPublished - 15 May 2018
EventThe 66th British Thyroid Association Annual Meeting - ELGAR CONCERT HALL, BRAMALL MUSIC BUILDING, UNIVERSITY OF BIRMINGHAM, , Birmingham, United Kingdom
Duration: 14 May 201815 May 2018


ConferenceThe 66th British Thyroid Association Annual Meeting
Country/TerritoryUnited Kingdom
Internet address


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