Searching the Resource Information Network
Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.
TGFβ signaling plays an important role in orchestrating a favorable microenvironment for tumor cell growth and promoting epithelial-mesenchymal transition. As a conventional nonsteroidal anti-inflammation drugs, tolfenamic acid (TA) has been previously reported to exhibit anti-cancer activity. Herein, we investigated the effect of TA on TGFβ-mediated pro-metastatic activity and the underlying mechanisms in hepatocellular carcinoma (HCC). As a result, TA suppresses TGFβ-induced migration and glycolysis in HCC cells, which is accompanied with reduced Smad phosphorylation and subsequent nuclear transcription activity. Mechanistically, TA promotes lipid raft-caveolar internalization pathway of TGFβ receptor, therefore leading to its rapid turnover. Consistently, TA inhibits constitutively active TGFβ type I receptor induced Smad phosphorylation and EMT markers, whereas ectopic expression of TGFβ type II receptor could partially rescue TGFβ-mediated Smad2 phosphorylation and downstream genes expression in the presence of TA. Furthermore, TA inhibited HCC cells invasion in nude mice, associated with the alteration of characteristics related with EMT and glycolysis of cancer cells. Our study suggests TA could activate lipid raft pathway and modulate TGFβ mediated metastasis, implicating the potential application of TA as a modulator of tumor microenvironment in HCC.
Pubmed ID: 31381904
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
A software for acquiring and analyzing flow cytometry data. The user can create plots with elements like regions, gates, statistics, markers, and annotated text. The software can also be used for batch analysis or quality control of analysis. Results can be exported and saved.
View all literature mentionsCell line Hep-G2 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SMMC-7721 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SK-HEP-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name NU/J from IMSR.
View all literature mentions