Dendrogenin A (DDA) is a tumor suppressor mammalian cholesterol-derived metabolite and a new class of ligand of the Liver X receptor (LXR), which displays tumor cell differentiation. In human and mouse breast adenocarcinoma cells, DDA-induced cell differentiation was associated with an increased accumulation of neutral lipids and proteins found in milk indicating that DDA re-activates some functions of lactating cells (de Medina et al, Nature Communications 2013). In the present study, we assessed whether DDA may induce other characteristic of lactating cells such as the expression of the sodium/iodide symporter (NIS) and iodine (I) uptake in breast cancer cells and extended this study to undifferentiated thyroid cancer cells. We report here that DDA induces NIS expression and significantly increases the uptake of radioactive iodine (131-I) by acting through the LXRβ, in all the cell lines tested.  In addition, the uptake of 131-I in the undifferentiated thyroid cancer cells was associated with a strong expression of all the specific proteins involved in thyroid hormone biosynthesis, TSH receptor, thyroperoxidase and thyroglobulin. Together these data show that the re-differentiation of breast and thyroid cancer cells by DDA, is associated with the recovery of functional NIS expression and involves an LXR-dependent mechanism. These results open new avenues of research for the diagnosis of thyroid cancers as well as the development of new therapeutic approaches for radioiodine refractory thyroid cancers.

Discover the published article :

PJ Steroid Biochem Mol Biol. 2019 Sep;192:105390.
The cholesterol-derived metabolite dendrogenin A functionally reprograms breast adenocarcinoma and undifferentiated thyroid cancer cells.
Bauriaud-Mallet M, Vija-Racaru L, Brillouet S, Mallinger A, de Medina P, Rives A, Payre B, Poirot M, Courbon F, Silvente-Poirot S.

Collaborations :
Affichem society , Nuclear Medicine IUCT-O, Toulouse

Keys words

• Dendrogenin A
• Tumor-suppressor
• Cholesterol metabolism
• Differentiation
• Breast cancer
• Thyroid cancer

Contact :

Sandrine Silvente-Poirot
Equipe 12, CRCT UMR1037

Mail : sandrine.poirot@inserm.fr