PBF interacts with cortactin and thyroglobulin in thyroid cells

Neil Sharma, Vicki Smith, Robert Seed, Martin Read, Gregory Lewy, Gavin Ryan, Jim Fong, Perkin Kwan, John C. Watkinson, Ashley Martin, Kristien Boelaert, Jayne Franklyn, Christopher McCabe

Research output: Contribution to journalAbstractpeer-review


PBF is a proto-oncogene implicated in the aetiology of thyroid cancer. Recently, we have shown that PBF binds NIS, MCT8 and p53, but the full spectrum of its interactions and physiological role within the thyroid remain unknown. Previously, we reported a shortlist of potential binding partners elucidated from K1 and TPC1 papillary thyroid carcinoma cells using tandem mass spectrometry (MS/MS, n=4). Here we present validation and characterisation of 2 of these proteins; thyroglobulin and cortactin. Cortactin, when activated, promotes rearrangement of the actin cytoskeleton and facilitates cell migration and endocytosis. Over-expression leads to the formation of invadopodia in cancer cells. Cortactin was identified in both K1 (peptides-10, score-413.3, sequence coverage-16.2%) and TPC1 cells (peptides-2, score-66.9, SC-7.5%). Immunofluorescence studies in TPC1 and K1 cells demonstrated that cortactin and PBF co-localise in intracellular vesicles, both within the cytoplasm and also in invadopodia projecting from the cell surface. Given that we have shown PBF to be trafficked to and from the cell surface, and to internalise NIS and MCT8 from the cell membrane, the interaction with cortactin may provide a mechanism for this action. Further experiments will examine the functional significance of this novel interaction in thyroid cancer, and also the role of PBF in invadopodia formation. Thyroglobulin binding was identified in K1 (peptides-5, score-192.0, SC-1.8%) and TPC1 cells (peptides-1, score-15.1, SC-0.3%). In our transgenic mouse model of PBF thyroidal over-expression, confocal microscopy demonstrated PBF to be present within the colloid of thyroid follicles, as well as at the apical membrane, supporting this finding. Furthermore, immunofluorescence in K1, TPC1 and SW1736 cells demonstrated co-localisation of PBF and thyroglobulin within intracellular vesicles. Taken together, the potential role of PBF in the transport of cellular proteins and its interaction with thyroglobulin may explain the phenotype of our transgenic mouse, which develops significantly enlarged thyroids.
Original languageEnglish
Article numberP338
JournalEndocrine Abstracts
Publication statusPublished - 2012
EventSociety for Endocrinology BES 2012 - Harrogate, United Kingdom
Duration: 18 Mar 201221 Mar 2012


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