2-cyano-3-12-dioxooleana-1-9(11)-dien-28-oic-acid-ethyl-amide and Liver-Neoplasms

RING-finger E3 ligases are instrumental in the regulation of inflammatory cascades, apoptosis, and cancer. However, their roles are relatively unknown in TGFβ/SMAD signaling. SMAD3 and its adaptors, such as β2SP, are important mediators of TGFβ signaling and regulate gene expression to suppress stem cell-like phenotypes in diverse cancers, including hepatocellular carcinoma (HCC). Here, PJA1, an E3 ligase, promoted ubiquitination and degradation of phosphorylated SMAD3 and impaired a SMAD3/β2SP-dependent tumor-suppressing pathway in multiple HCC cell lines. In mice deficient for SMAD3 (

Topics: Animals; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; Down-Regulation; Exome Sequencing; Gene Deletion; Gene Expression Regulation; Gene Knockdown Techniques; Gene Silencing; Heterografts; Humans; Liver Neoplasms; Mice; Mice, Nude; Neoplastic Stem Cells; Oleanolic Acid; Phosphorylation; RNA, Small Interfering; Smad Proteins; Smad2 Protein; Smad3 Protein; Spectrin; Stem Cells; Transforming Growth Factor beta; Transforming Growth Factor beta1; Ubiquitin-Protein Ligases; Ubiquitination; Up-Regulation