IM-412 inhibits the invasion of human breast carcinoma cells by blocking FGFR-mediated signaling

Oncology Reports
Seung-Youn JungJie-Young Song

Abstract

Triple-negative breast cancer (TNBC) is an aggressive cancer with a poor prognosis due to its epithelial‑to-mesenchymal transition (EMT) phenotype. Cancer patients often experience several detrimental effects of cancer treatment, such as chemoresistance, radioresistance and the maintenance of cancer stem cells due to EMT. Thus, EMT signaling is considered to be a valuable therapeutic target for cancer treatment, and its inhibition is being attempted as a new treatment option for TNBC patients. Previously, we showed that 3-(2-chlorobenzyl)-1,7-dimethyl-1H-imidazo[2,1-f]purine‑2,4(3H,8H)-dione (IM-412) inhibits transforming growth factor-β (TGF-β)-induced differentiation of human lung fibroblasts through both Smad-dependent and -independent pathways. In the present study, we examined the inhibitory effect of IM-412 on EMT pathways and invasiveness in TNBC cells since the TGF-β signaling pathway is a typical signaling pathway that functions in EMT. IM-412 not only potently suppressed the migration and invasion of MDA-MB-231 cells, but also lowered the expression of mesenchymal markers and EMT-activating transcription factors in these cells. IM-412 inhibited the activation of several signaling proteins, including Smad2/Smad3, p38MA...Continue Reading

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Citations

Jun 30, 2019·The Journal of Pharmacology and Experimental Therapeutics·Seung-Youn JungJie-Young Song
Dec 20, 2015·Anti-cancer Drugs·Lee Yueh JiaAnupam Bishayee
Nov 7, 2019·Journal of Cellular and Molecular Medicine·Mi-Hyoung KimJie-Young Song
Oct 11, 2019·Journal of breast cancer·Maryam NakhjavaniAmanda R Townsend
Jan 12, 2021·Molecular Carcinogenesis·Naing L ShanNanjoo Suh

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