TIAF1 self‐aggregation causes spontaneous activation of SMAD‐responsive promoter in p53‐deficient environment and cell death
Abstract
Self‐aggregation of TGF‐beta‐induced antiapoptotic factor (TIAF1) is known in the nondemented human hippocampus, and the aggregating process may lead to generation of amyloid beta (Abeta) for causing neurodegeneration. Here, we determined that solid tumors frequently overexpress TIAF1, which exhibits as aggregates together with Smad4 and Abeta in the cancer stroma and peritumor capsules. Also, TIAF1/Abeta aggregates are shown on the interface between neural cells and the metastatic cancer cell mass. In vitro induction of TIAF1 self‐association upregulated the expression of tumor suppressors Smad4 and WOX1 (or WWOX), and WOX1 in turn increased the TIAF1 expression. TIAF1/Smad4 interaction further generated Abeta. TIAF1 suppresses SMAD‐regulated promoter activation. Intriguingly, without p53, TIAF1 self‐association spontaneously activated the SMAD‐regulated promoter. TIAF1 was shown to be essential for p53‐, WOX1‐ and dominant negative JNK1‐induced cell death. Indeed, TIAF1, p53 and WOX1 acted synergistically in suppressing anchorage‐independent growth and causing apoptosis. Together, TIAF1 shows an aggregation‐dependent control of tumor progression and metastasis, and regulation of cell death. (supported by NSC and NHRI, Taiwan and DoD, USA)
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2012
- Source ID
- 10.1096/fasebj.26.1_supplement.797.3
Entities
People
- Nan-Shan Chang
Organizations
- National Cheng Kung University
- National Science and Technology Council
- United States Department of Defense