A novel cell-penetrating peptide suppresses breast tumorigenesis by inhibiting beta-catenin/LEF-1 signaling

作者：Hsieh Tsung Hua; Hsu Chia Yi; Tsai Cheng Fang; Chiu Chien Chih; Liang Shih Shin; Wang Tsu Nai; Kuo Po Lin; Long Cheng Yu; Tsai Eing Mei^*

来源：Scientific Reports, 2016, 6(1): 19156.

DOI：10.1038/srep19156

The inhibition of beta-catenin/LEF-1 signaling is an emerging strategy in cancer therapy. However, clinical targeted treatment of the beta-catenin/LEF-1 complex remains relatively ineffective. Therefore, development of specific molecular targets is a key approach for identifying new cancer therapeutics. Thus, we attempted to synthesize a peptide (TAT-NLS-BLBD-6) that could interfere with the interaction of beta-catenin and LEF-1 at nuclei in human breast cancer cells. TAT-NLS-BLBD-6 directly interacted with beta-catenin and inhibited breast cancer cell growth, invasion, migration, and colony formation as well as increased arrest of sub-G1 phase and apoptosis; it also suppressed breast tumor growth in nude mouse and zebrafish xenotransplantation models, showed no signs of toxicity, and did not affect body weight. Furthermore, the human global gene expression profiles and Ingenuity Pathway Analysis software showed that the TAT-NLS-BLBD-6 downstream target genes were associated with the HER-2 and IL-9 signaling pathways. TAT-NLS-BLBD-6 commonly down-regulated 27 candidate genes in MCF-7 and MDA-MB-231 cells, which are concurrent with Wnt downstream target genes in human breast cancer. Our study suggests that TAT-NLS-BLBD-6 is a promising drug candidate for the development of effective therapeutics specific for Wnt/beta-catenin signaling inhibition.

• 出版日期2016-1-11
• 单位河北医科大学