Knockdown of lymphoid enhancer factor 1 inhibits colon cancer progression in vitro and in vivo.

Abstract

Expression of lymphoid enhancer factor 1 (LEF1) is frequently altered in different human cancers. This study aimed to assess LEF1 expression in colon cancer tissues and to explore changed phenotypes, gene expressions, and the possible mechanism after knocked down LEF1 expression in colon cancer cell lines. A total of 106 colon cancer and matched paratumorous normal tissues were used to assess LEF1 expression using immunohistochemistry and qRT-PCR. LEF1 lentivirus was used to knockdown LEF1 expression for the assessment of cell viability, cell cycle distribution, apoptosis, and gene expressions. The nude mouse xenograft assay was performed to detect the effects of LEF1 knockdown in vivo. The data showed that the levels of LEF1 mRNA and protein were significantly increased in human colon cancer tissues compared to the matched paratumorous normal tissues and were associated with infiltration depth, lymph node and distant metastases, advanced TNM (tumor-node-metastasis) stages, and shorter overall survival. Furthermore, LEF1 knockdown reduced tumor cell viability, invasion capacity, MMP2 and MMP-9 expression, but induced apoptosis. Nude mouse xenograft assay showed that LEF1 knockdown suppressed tumor formation and growth in vivo. In addition, the expression of Notch pathway-related proteins RBP-jκ and Hes1 was reduced in LEF1 knockdown cells. Taken together, LEF1 protein was overexpressed in colon cancer tissues and knockdown of LEF1 expression inhibited colon cancer growth in vitro and in vivo. These data suggest that targeting of LEF1 expression should be further evaluated for colon cancer prevention and therapy.

• Authors: Wen-Juan Wang, Yu Yao, Li-Li Jiang, Ting-Hua Hu, Jie-Qun Ma, Zi-Jun Liao, Jun-Tao Yao, Dong-Fan Li, Shu-Hong Wang, Ke-Jun Nan
• Journal: PloS one (PLoS One) Vol. 8 Issue 10 Pg. e76596 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 24098538 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Basic Helix-Loop-Helix Transcription Factors
• Homeodomain Proteins
• Immunoglobulin J Recombination Signal Sequence-Binding Protein
• LEF1 protein, human
• Lymphoid Enhancer-Binding Factor 1
• RBPJ protein, human
• Transcription Factor HES-1
• HES1 protein, human
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9

Topics

• Adult
• Aged
• Aged, 80 and over
• Animals
• Apoptosis (genetics)
• Basic Helix-Loop-Helix Transcription Factors (genetics, metabolism)
• Colonic Neoplasms (genetics, metabolism, pathology)
• Female
• Gene Expression Regulation, Neoplastic
• Genetic Vectors
• Homeodomain Proteins (genetics, metabolism)
• Humans
• Immunoglobulin J Recombination Signal Sequence-Binding Protein (genetics, metabolism)
• Lentivirus (genetics)
• Lymphatic Metastasis
• Lymphoid Enhancer-Binding Factor 1 (antagonists & inhibitors, genetics, metabolism)
• Male
• Matrix Metalloproteinase 2 (genetics, metabolism)
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Mice
• Mice, Nude
• Middle Aged
• Neoplasm Transplantation
• Signal Transduction
• Transcription Factor HES-1