TIAF1 self-aggregation in peritumor capsule formation, spontaneous activation of SMAD-responsive promoter in p53-deficient environment, and cell death

J. Y. Chang, M. F. Chiang, S. R. Lin, M. H. Lee, H. He, P. Y. Chou, Shean-Jen Chen, Y. A. Chen, L. Y. Yang, F. J. Lai, C. C. Hsieh, T. H. Hsieh, H. M. Sheu, C. I. Sze, N. S. Chang*

*Corresponding author for this work

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Self-aggregation of transforming growth factorβ (TGF-β)1-induced antiapoptotic factor (TIAF1) is known in the nondemented human hippocampus, and the aggregating process may lead to generation of amyloid β (Aβ) for causing neurodegeneration. Here, we determined that overexpressed TIAF1 exhibits as aggregates together with Smad4 and Aβ in the cancer stroma and peritumor capsules of solid tumors. Also, TIAF1/Aβ aggregates are shown on the interface between brain neural cells and the metastatic cancer cell mass. TIAF1 is upregulated in developing tumors, but may disappear in established metastatic cancer cells. Growing neuroblastoma cells on the extracellular matrices from other cancer cell types induced production of aggregated TIAF1 and Aβ. In vitro induction of TIAF1 self-association upregulated the expression of tumor suppressors Smad4 and WW domain-containing oxidoreductase (WOX1 or WWOX), and WOX1 in turn increased the TIAF1 expression. TIAF1/Smad4 interaction further enhanced Aβ formation. TIAF1 is known to suppress SMAD-regulated promoter activation. Intriguingly, without p53, self-aggregating TIAF1 spontaneously activated the SMAD-regulated promoter. TIAF1 was essential for p53-, WOX1- and dominant-negative JNK1-induced cell death. TIAF1, p53 and WOX1 acted synergistically in suppressing anchorageindependent growth, blocking cell migration and causing apoptosis. Together, TIAF1 shows an aggregation-dependent control of tumor progression and metastasis, and regulation of cell death.

Original languageEnglish
Article numbere302
JournalCell Death and Disease
Volume3
Issue number4
DOIs
StatePublished - 1 Apr 2012

Keywords

  • Smad4
  • TGF-β
  • TIAF1
  • WOX1
  • WWOX
  • p53

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    Chang, J. Y., Chiang, M. F., Lin, S. R., Lee, M. H., He, H., Chou, P. Y., Chen, S-J., Chen, Y. A., Yang, L. Y., Lai, F. J., Hsieh, C. C., Hsieh, T. H., Sheu, H. M., Sze, C. I., & Chang, N. S. (2012). TIAF1 self-aggregation in peritumor capsule formation, spontaneous activation of SMAD-responsive promoter in p53-deficient environment, and cell death. Cell Death and Disease, 3(4), [e302]. https://doi.org/10.1038/cddis.2012.36