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The role of ATP-binding cassette transporter genes in the metastatic process of epithelial thyroid carcinoma with aggressive behavior

Abstract:

There is a strong association between the increased expression of ATP-binding cassette (ABC) transporters, multidrug resistant tumors, and worse prognoses. This chapter summarizes the roles of ABCB1, ABCC1, and ABCG2 in the dedifferentiation, refractoriness, and epithelial-mesenchymal transition (EMT) processes in epithelial thyroid cancer (ETC). Although the molecular mechanisms involved in the EMT associated with resistant tumors remain poorly understood, the major inducers—HIF-1, NF-κB, TGF-β, Snail, SOX2, MSX, ZEB1, Twist, and Snail1—together with the PI3K/Akt, MAPK, Hedgehog, Wnt/β-catenin, Notch, and Hippo signaling pathways, have been identified as critical in the ETC malignancy process. Moreover, the tyrosine kinase inhibitors, used as therapeutic strategies in radioactive iodine I-131 (RAI) refractory thyroid carcinomas and aggressive tumors, are actively transported through these ABC transporters and can play a critical role in the chemoresistance of some ETC subtypes.