Sdhd ablation promotes thyroid tumorigenesis by inducing a stem-like phenotype

We report that these mice develop enlarged thyroid glands with follicle hypercellularity and increased proliferation. In vitro, human thyroid cell lines with knockdown of SDHD exhibit an enhanced migratory capability, despite no change in proliferative capacity. Interestingly, these cells acquire stem-like features which are also observed in the mouse tumors. The stem-like characteristics are reversed by α-ketoglutarate, suggesting that SDH-associated tumorigenesis results from dedifferentiation driven by an imbalance in cellular metabolites of the TCA cycle. The results of this study reveal a metabolic vulnerability for potential future treatment of SDH-associated neoplasia.

Source: Endocrine-Related Cancer - October 20, 2017 Category: Endocrinology Authors: Ashtekar, A., Huk, D., Magner, A., La Perle, K., Zhang, X., Piruat, J. I., Lopez-Barneo, J., Jhiang, S. M., Kirschner, L. S. Tags: Research Source Type: research