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Carcinogenesis Advance Access published online on October 20, 2009
Carcinogenesis, doi:10.1093/carcin/bgp251
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Abl Interactor 1 Regulates Src-Id1-Matrix Metalloproteinase 9 Axis and Is Required for Invadopodia Formation, Extracellular Matrix Degradation, and Tumor Growth of Human Breast Cancer Cells

Xiaolin Sun*,1,3, Chenghai Li*,1, Chunmei Zhuang*,1,4, William C. Gilmore5, Everardo Cobos1,2, Yunxia Tao1 and Zonghan Dai1,2

1 Department of Internal Medicine
2 Stem Cell Transplant Program, Texas Tech University Health Sciences Center, Amarillo, Texas
3 State Key Lab for Agro-Biotechnology, College of Biological Sciences, China Agricultural University, Beijing, China
4 State Key Laboratory of Microbial Technology, Shandong University, Jinan, China
5 The Texas Veterinary Medical Diagnostic Laboratories, Amarillo, Texas

Correspondence author: Zonghan Dai, Department of Internal Medicine, Texas Tech University Health Sciences Center, 1406 Coulter Street, Amarillo, TX 79106. Phone: 806-356-4757x243; Fax: 806-354-5669; E-mail: Zonghan.dai{at}ttuhsc.edu

Abl interactor 1 (Abi1) is a key regulator of actin polymerization/depolymerization. The involvement of Abi1 in the development of abnormal cytoskeletal functions of cancer cells has recently been reported. It remains unclear, however, how Abi1 exerts its effects in tumor cells and whether it contributes to tumor progression in vivo. We report here a novel function for Abi1 in the regulation of invadopodia formation and Src-Id1-matrix metalloproteinase 9 (MMP-9) pathway in MDA-MB231 human breast cancer cells. Abi1 is found in the invadopodia of MDA-MB231 cells. Epigenetic silencing of the Abi1 gene by short hairpin RNA (shRNA) in MDA-MB231 cells impaired the formation of invadopodia and resulted in down-regulation of the Scr activation and Id1/MMP-9 expression. The decreased invadopodia formation and MMP-9 expression correlate with a reduction in the ability of these cells to degrade extracellular matrix (ECM). Remarkably, the knockdown of Abi1 expression inhibited tumor cell proliferation and migration in vitro, and slowed tumor growth in vivo. Taken together, these results indicate that the Abi1 signaling plays a critical role in breast cancer progression and suggest that this pathway may serve as a therapeutic target for the treatment of human breast cancer.

Key Words: Abi1/Src/Id1 /MMP-9/ invadopodia

* These authors contributed equally to this work

Received January 12, 2009; revised October 9, 2009; accepted October 12, 2009.


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