TGF-β downregulation-induced cancer cell death is finely regulated by the SAPK signaling cascade

Abstract

Cancer: Tipping the signaling balance Reducing the levels of the multifunctional protein transforming growth factor (TGF)-β in cancer cells prevents tumor growth in mice. Previous studies have shown that high levels of TGF-β in cancerous tissue are associated with accelerated disease progression. Hye Jin Choi and Jae J Song at Yonsei University in Seoul, South Korea, and colleagues infected cancer cells with genetically modified viruses that reduced the expression of the gene encoding TGF-β. The resulting decrease in TGF-β protein led to cell death by stimulating the production of reactive oxygen species and signaling through the apoptosis signal-regulating kinase 1 (ASK1) pathway. When tumor-bearing mice were infected with these modified viruses, their overall survival was improved. Further understanding the mechanisms through which TGF-β regulates cancer cell survival will contribute to the development of new approaches in cancer treatment.