TCF-4 (T cell factor-4) is a member of the TCF/LEF (lymphoid enhancer factor) family of transcription factors. Although dysregulation of β-catenin is decisive for the initiation and progression of colorectal cancer, the role of TCF4 in transcriptional regulation of their target gene remained poorly understood. The current study was performed to see if TCF4 could be molecular target for anti-cancer compounds. Several phytochemicals including resveratrol repressed expression of TCF4 in human colorectal cancer cells. Resveratrol decreases accumulation of ectopically expressed TCF4 protein without changes of TCF4 transcription. Pre-treatment of MG-132 and lactacystin ameliorates resveratrol-stimulated downregulation of TCF4. Resveratrol-treated cells showed longer half-life of TCF4. Resveratrol increased phosphorylation of TCF4 at serine/threonine residues through ERK and p38-dependent pathways. Knockdown of TCF4 decreased TCF/β-catenin-mediated transcriptional activity and sensitized resveratrol-induced apoptosis. The current study provides new mechanistic link between TCF4 downregulation and significant benefits of phytochemicals.
Citation Format: Jin Boo Jeong, Kui-Jin Kim, Seong-Ho Lee. TCF4 is a molecular target of resveratrol-induced apoptosis in colon cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4564. doi:10.1158/1538-7445.AM2015-4564