• 作者：Ana Lopez-Campistrous^a ; Esther Ekpe Adewuyi^a ; Matthew G.K. Benesch^b ; Yi Man Ko^a ; Raymond Lai^c ; Aducio Thiesen^c ; Jay Dewald^b ; Peng Wang^d ; Karen Chu^e ; Sunita Ghosh^e ; David C. Williams^a ; Larissa J. Vos^e ; David N. Brindley^b ; Todd P.W. McMullen^a ; ^e ; ^{todd.mcmullen@ualberta.ca" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Platelet derived growth factor receptor ; Metastases ; Papillary thyroid cancer ; TTF1(Nkx2-1)
• 刊名：EBioMedicine
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：12
• 期：Complete
• 页码：86-97
• 全文大小：1834 K

•

PDGFRα induces dedifferentiation of papillary thyroid cancer cells.

•

This depends on decreased phosphorylation and decreased nuclear targeting of TTF1.

•

Loss of nuclear TTF1 decreases thyroglobulin production and NaI transport.

•

PDGFRα expression is prognostic of PTC recurrence and treatment resistance.

•

Blocking PDGFRα activation is a potential therapeutic target.

Treatment of papillary thyroid cancer historically relied upon a combination of surgery and radioactive iodine ablation with few alternatives if the disease progresses. We found that platelet derived growth factor receptor alpha (PDGFRα) is a key driver of metastatic disease and resistance to radioactive iodine therapy. PDGFRα expression can be tested in tumor specimens to predict aggressive disease. In addition, we show that targeting PDGFRα could restore sensitivity to radioactive iodine treatment that might slow disease growth and spread.