Targeting Transforming Growth Factor-Beta1 (TGF-β1) Inhibits Tumorigenesis of Anaplastic Thyroid Carcinoma Cells Through ERK1/2-NFκkB-PUMA Signaling

Abstract

BackgroundThe transforming growth factor-beta (TGF-β) signaling pathway plays a critical role in promoting tumor growth. TGF-β1was found to be overexpressed in anaplastic thyroid cancer (ATC). We therefore tested our hypothesis that targeting TGF-β1 inhibits tumorigenesis of ATC cells.Material/MethodsEffects of TGF-β1 stimulation or TGF-β1 inhibition by small interfering RNA (TGF-β1siRNA) on proliferation, colony formation, and apoptosis in 8505C cells in vitro was detected using siRNAs and inhibitors to examine the TGF-β1 signaling pathway. A subcutaneously implanted tumor model of 8505C cells in nude mice was used to assess the effects of TGF-β1 inhibition on tumorigenesis development.ResultsTGF-β1siRNAs decreased proliferation and colony formation, and increased apoptosis in 8505C cells in vitro and inhibited tumor growth in vivo. TGF-β1siRNA inhibited phosphorylation ERK1/2 (pERK1/2) and increased p65-dependant PUMA mRNA and protein expression. Knockdown of p65 or PUMA by siRNA reduced TGF-β1siRNA-induced apoptosis, as well as caspase-3 and PARP activation. Upregulation of p65 or PUMA expression by TGF-β1siRNA requires pERK1/2 inhibition. TGF-β1 shRNA inhibited tumor growth in vivo.ConclusionsTherapies targeting the TGF-β1 pathway may be more effective to prevent primary tumor formation. The ability of this therapy to decrease tumorigenesis may be related to ERK1/2/NF-κB/PUMA signaling.

WITHDRAWN: Contribution of microRNA-30d to the prevention of the thyroid cancer progression: mechanism and implications

“…Recent literature has identified that SIRT1 can deacetylate and modify the transcription factor FOXO3a to control the expression of PUMA [22], which functions as a tumor suppressor gene in the pathogenesis of thyroid cancer through enhancing apoptosis [23]. We herein aimed to determine whether SIRT1 affected the apoptosis of thyroid cancer cells through modulating the acetylation level of FOXO3a and its enrichment in the PUMA promoter.…”

Effects of miR-144 on the sensitivity of human anaplastic thyroid carcinoma cells to cisplatin by autophagy regulation

“…was also frequently seen. [35][36][37][38][39] Furthermore, TGF-GFhas been found to be associated with cisplatin-resistant neoplasms. [40][41][42] As a transforming growth factor, TGF-a has not been thoroughly studied in thyroid carcinoma especially ATC with cisplatin-resistance, remaining a gap field of thyroid carcinoma.…”

Mammalian Target of Rapamycin (mTOR) Regulates Transforming Growth Factor-β1 (TGF-β1)-Induced Epithelial-Mesenchymal Transition via Decreased Pyruvate Kinase M2 (PKM2) Expression in Cervical Cancer Cells

“…Large studies indicated that the EMT was induced by transforming growth factor β 1 (TGF-β 1 ) in various cancer cells [ 8 , 9 ]. Yin et al reported that TGF-β 1 was overexpressed in anaplastic thyroid cancer, and they found that knockdown of TGF-β 1 could inhibited cell proliferation and colony formation, and promoted apoptosis in anaplastic thyroid cells [ 10 ]. Park et al found that TGF-β 1 promotes cancer immune escape, and that it promoted cell proliferation, colony formation, and inhibited apoptosis [ 11 ].…”