Authors

Jing-yao Dai, Cell Engineering Research Centre & Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, No.17 West Changle Road, Xi'an 710032, Shaanxi, PR China, Department of Hepatobiliary Surgery, First Affiliated Hospital, Fourth Military Medical University, No.17 West Changle Road, Xi'an 710032, Shaanxi, PR ChinaFollow
Ke-feng Dou, Department of Hepatobiliary Surgery, First Affiliated Hospital, Fourth Military Medical University, No.17 West Changle Road, Xi'an 710032, Shaanxi, PR ChinaFollow
Cong-hua Wang, Department of Clinical Immunology, First Affiliated Hospital, Fourth Military Medical University, No.17 West Changle Road, Xi'an 710032, Shaanxi, PR ChinaFollow
Pu Zhao, Cell Engineering Research Centre & Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, No.17 West Changle Road, Xi'an 710032, Shaanxi, PR ChinaFollow
Wayne Bond Lau, Department of Emergency Medicine, Thomas Jefferson University, 1015 Walnut Street, Philadelphia, PA, 19107, USAFollow
Ling Tao, Department of Cardiology, First Affiliated Hospital, Fourth Military Medical University, No.17 West Changle Road, Xi'an 710032, Shaanxi, PR ChinaFollow
Ya-mei Wu, Cell Engineering Research Centre & Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, No.17 West Changle Road, Xi'an 710032, Shaanxi, PR ChinaFollow
Juan Tang, Cell Engineering Research Centre & Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, No.17 West Changle Road, Xi'an 710032, Shaanxi, PR ChinaFollow
Jian-li Jiang, Cell Engineering Research Centre & Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, No.17 West Changle Road, Xi'an 710032, Shaanxi, PR ChinaFollow
Zhi-nan Chen, Cell Engineering Research Centre & Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, No.17 West Changle Road, Xi'an 710032, Shaanxi, PR ChinaFollow

Document Type

Article

Publication Date

1-1-2009

Comments

This article has been peer reviewed and is published in BMC Cancer Volume 9, 23 September 2009, Article number 1471, Page 337. The published version is available at DOI: 10.1186/1471-2407-9-337. Copyright © BioMed Central Ltd.

Abstract

BACKGROUND: HAb18G/CD147 plays pivotal roles in invasion by hepatoma cells, but the underlying mechanism remains unclear. Our previous study demonstrated that overexpression of HAb18G/CD147 promotes invasion by interacting with integrin alpha3beta1. However, it has never been investigated whether alpha3beta1 is solely responsible for this process or if other integrin family members also interact with HAb18G/CD147 in human hepatoma cells. METHODS: Human SMMC-7721 and FHCC98 cells were cultured and transfected with siRNA fragments against HAb18G/CD147. The expression levels of HAb18G/CD147 and integrin alpha6beta1 were determined by immunofluorescent double-staining and confocal imaging analysis. Co-immunoprecipitation and Western blot analyses were performed to examine the native conformations of HAb18G/CD147 and integrin alpha6beta1. Invasion potential was evaluated with an invasion assay and gelatin zymography. RESULTS: We found that integrin alpha6beta1 co-localizes and interacts with HAb18G/CD147 in human hepatoma cells. The enhancing effects of HAb18G/CD147 on invasion capacity and secretion of matrix metalloproteinases (MMPs) were partially blocked by integrin alpha6beta1 antibodies (P < 0.01). Wortmannin, a specific phosphatidylinositol kinase (PI3K) inhibitor that reverses the effect of HAb18G/CD147 on the regulation of intracellular Ca2+ mobilization, significantly reduced cell invasion potential and secretion of MMPs in human hepatoma cells (P < 0.05). Importantly, no additive effect between Wortmannin and alpha6beta1 antibodies was observed, indicating that alpha6beta1 and PI3K transmit the signal in an upstream-downstream relationship. CONCLUSION: These results suggest that alpha6beta1 interacts with HAb18G/CD147 to mediate tumor invasion and metastatic processes through the PI3K pathway.

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