Research article summary (published 29 Nov 2009):

Id-1 promotes tumorigenicity and metastasis of human esophageal cancer cells through activation of PI3K/AKT signaling pathway.

Full Abstract

Id-1 (inhibitor of differentiation or DNA binding) is a helix-loop-helix protein that is overexpressed in many types of cancer including esophageal squamous cell carcinoma (ESCC). We previously reported that ectopic Id-1 expression activates the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in human esophageal cancer cells. In this study, we confirmed a positive correlation between Id-1 and phospho-AKT (Ser473) expressions in ESCC cell lines, as well as in ESCC on a tissue microarray. To investigate the significance of Id-1 in esophageal cancer progression, ESCC cells with stable ectopic Id-1 expression were inoculated subcutaneously into the flank of nude mice and were found to form larger tumors that showed elevated Ki-67 proliferation index and increased angiogenesis, as well as reduced apoptosis, compared with control cells expressing the empty vector.The Id-1-overexpressing cells also exhibited enhanced metastatic potential in the experimental metastasis assay. Treatment with the PI3K inhibitor LY294002 attenuated the tumor promotion effects of Id-1, indicating that the effects were mediated by the PI3K/AKT signaling pathway. In addition, our in vitro experiments showed that ectopic Id-1 expression altered the expression levels of markers associated with epithelial-mesenchymal transition and enhanced the migration ability of esophageal cancer cells. The Id-1-overexpressing ESCC cells also exhibited increased invasive potential, which was in part due to PI3K/AKT-dependent modulation of matrix metalloproteinase-9 expression. In conclusion, our results provide the first evidence that Id-1 promotes tumorigenicity and metastasis of human esophageal cancer in vivo and that the PI3K inhibitor LY294002 can attenuate these effects.

Author information

Author/s: Li, Bin (B); Tsao, Sai Wah (SW); Li, Yuk Yin (YY); Wang, Xianghong (X); Ling, Ming Tat (MT); Wong, Yong Chuan (YC); He, Qing Yu (QY); Cheung, Annie L M (AL);

Affiliation: Cancer Biology Group, Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: International journal of cancer. Journal international du cancer (Int J Cancer), published in United States. (Language: eng)

Reference: 2009-Dec; vol 125 (issue 11) : pp 2576-85

Dates: Created 2009/10/05; Completed 2009/11/06;

PMID: 19551863, status: MEDLINE (last retrieval date: 11/6/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

1-Phosphatidylinositol 3-Kinase - metabolism Animals Apoptosis Blotting, Western Carcinoma, Squamous Cell - metabolism; pathology Cell Movement Cell Proliferation Esophageal Neoplasms - metabolism; pathology Female Fluorescent Antibody Technique Humans

Immunoenzyme Techniques Inhibitor of Differentiation Protein 1 - physiology Mice Mice, Inbred BALB C Mice, Nude Neoplasm Invasiveness Proto-Oncogene Proteins c-akt - metabolism Signal Transduction Tumor Cells, Cultured Wound Healing Xenograft Model Antitumor Assays

Associated Chemicals: ID1 protein, human (0) ; Inhibitor of Differentiation Protein 1 (0) ; 1-Phosphatidylinositol 3-Kinase (EC 2.7.1.137) ; Proto-Oncogene Proteins c-akt (EC 2.7.1.37)

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