PUBLICATION
A novel cell-penetrating peptide suppresses breast tumorigenesis by inhibiting β-catenin/LEF-1 signaling
- Authors
- Hsieh, T.H., Hsu, C.Y., Tsai, C.F., Chiu, C.C., Liang, S.S., Wang, T.N., Kuo, P.L., Long, C.Y., Tsai, E.M.
- ID
- ZDB-PUB-160113-12
- Date
- 2016
- Source
- Scientific Reports 6: 19156 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Apoptosis/drug effects
- Breast Neoplasms/genetics
- Breast Neoplasms/metabolism*
- Breast Neoplasms/pathology*
- Cell Line, Tumor
- Cell Movement/drug effects
- Cell Nucleus/metabolism
- Cell Proliferation/drug effects
- Cell Transformation, Neoplastic/metabolism*
- Cell-Penetrating Peptides/metabolism*
- Cell-Penetrating Peptides/pharmacology
- Disease Models, Animal
- Female
- Gene Expression Regulation, Neoplastic
- Humans
- Lymphoid Enhancer-Binding Factor 1/metabolism*
- Mice
- Mice, Nude
- Nuclear Localization Signals/chemistry
- Nuclear Localization Signals/metabolism
- Protein Binding
- Recombinant Fusion Proteins/metabolism
- Recombinant Fusion Proteins/pharmacology
- Signal Transduction*/drug effects
- Xenograft Model Antitumor Assays
- Zebrafish
- beta Catenin/metabolism*
- tat Gene Products, Human Immunodeficiency Virus/chemistry
- tat Gene Products, Human Immunodeficiency Virus/metabolism
- PubMed
- 26750754 Full text @ Sci. Rep.
Citation
Hsieh, T.H., Hsu, C.Y., Tsai, C.F., Chiu, C.C., Liang, S.S., Wang, T.N., Kuo, P.L., Long, C.Y., Tsai, E.M. (2016) A novel cell-penetrating peptide suppresses breast tumorigenesis by inhibiting β-catenin/LEF-1 signaling. Scientific Reports. 6:19156.
Abstract
The inhibition of β-catenin/LEF-1 signaling is an emerging strategy in cancer therapy. However, clinical targeted treatment of the β-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 β-catenin and LEF-1 at nuclei in human breast cancer cells. TAT-NLS-BLBD-6 directly interacted with β-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/β-catenin signaling inhibition.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping