Abstract B3: Induction of Smad4 in response to serum starvation promotes cell death through PUMA stabilization

• Published in: Cancer research (Chicago, Ill.) Vol. 71; no. 18_Supplement; p. B3
• Main Authors: Lee, Sun-Hye, Jung, Youn-Sang, Chung, Ji-Yun, Oh, Ah-Young, Lee, Su-Jin, Park, Bum-Joon
• Format: Journal Article
• Language: English
• Published: 15-09-2011
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.FBCR11-B3

Smad4 is an essential factor in TGF-β signaling and is also known as frequently mutated tumor suppressor gene in human pancreatic and colon cancer. However, considering the fact that TGF-β can contribute to cancer progression through transcriptional target genes such as Snail, MMPs, and EMT-related genes, loss of Smad4 in human cancer would be required for obtaining the TGF-β signaling independent advantage, which should be essential for cancer cell survival. Here we provide the evidence about novel role of Smad4, serum-deprivation-induced apoptosis. Elimination of serum can obviously increase the Smad4 expression and induces the cell death by p53-independent PUMA induction. Instead, Smad4 deficient cells show the resistance to serum starvation. Induced Smad4 suppresses the PAK1, which promotes the PUMA destabilization. We also found that siah-1 and pVHL are involved in PAK1 destabilization and PUMA stabilization. In fact, Smad4-expressed cancer tissues show the elevated expression of PAK1, also supprots our hypothesis that Smad4 induces PUMA-mediated cell death through PAK1 suppression. Our results strongly suggest that loss of Smad4 render the resistance to serum-deprivation-induced cell death, which is the TGF-β independent tumor suppressive role of Smad4.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B3.