This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yang, X. H. Articles by Hemler, M. E. Search for Related Content PubMed PubMed Citation Articles by Yang, X. H. Articles by Hemler, M. E.

CD151 Accelerates Breast Cancer by Regulating ₆ Integrin Function, Signaling, and Molecular Organization

Departments of ¹ Cancer Immunology and AIDS, ² Medical Oncology, and ³ Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School; ⁴ Department of Pathology, Brigham and Women's Hospital and Harvard Medical School; and ⁵ Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts

Requests for reprints: Martin E. Hemler, Dana-Farber Cancer Institute, Room D1430, 44 Binney Street, Boston, MA 02115. Phone: 617-632-3410; Fax: 617-632-2662; E-mail: Martin_Hemler{at}DFCI.Harvard.EDU or Xiuwei Yang, Dana-Farber Cancer Institute, Room D1430, 44 Binney Street, Boston, MA 02115. Phone: 617-632-3280; Fax: 617-632-2662; E-mail: Xiuwei_Yang{at}DFCI.Harvard.EDU.

Key Words: CD151 • integrins • Breast cancer • Cell adhesion and extracellular matrix • Cell motility and migration • Tumor Progression, Invasion, and Metastasis • Growth factor receptors and other surface molecules as targets for therapy

CD151, a master regulator of laminin-binding integrins (₆β₄, ₆β₁, and ₃β₁), assembles these integrins into complexes called tetraspanin-enriched microdomains. CD151 protein expression is elevated in 31% of human breast cancers and is even more elevated in high-grade (40%) and estrogen receptor–negative (45%) subtypes. The latter includes triple-negative (estrogen receptor, progesterone receptor, and HER2 negative) basal-like tumors. CD151 ablation markedly reduced basal-like mammary cell migration, invasion, spreading, and signaling (through FAK, Rac1, and lck) while disrupting epidermal growth factor receptor (EGFR)-₆ integrin collaboration. Underlying these defects, CD151 ablation redistributed ₆β₄ integrins subcellularly and severed molecular links between integrins and tetraspanin-enriched microdomains. In a prototypical basal-like mammary tumor line, CD151 ablation notably delayed tumor progression in ectopic and orthotopic xenograft models. These results (a) establish that CD151-₆ integrin complexes play a functional role in basal-like mammary tumor progression; (b) emphasize that ₆ integrins function via CD151 linkage in the context of tetraspanin-enriched microdomains; and (c) point to potential relevance of CD151 as a high-priority therapeutic target, with relative selectivity (compared with laminin-binding integrins) for pathologic rather than normal physiology. [Cancer Res 2008;68(9):3204–13]

This article has been cited by other articles:

				J. L. Johnson, N. Winterwood, K. A. DeMali, and C. S. Stipp Tetraspanin CD151 regulates RhoA activation and the dynamic stability of carcinoma cell-cell contacts J. Cell Sci., July 1, 2009; 122(13): 2263 - 2273. [Abstract] [Full Text] [PDF]

				R. Sadej, H. Romanska, G. Baldwin, K. Gkirtzimanaki, V. Novitskaya, A. D. Filer, Z. Krcova, R. Kusinska, J. Ehrmann, C. D. Buckley, et al. CD151 Regulates Tumorigenesis by Modulating the Communication between Tumor Cells and Endothelium Mol. Cancer Res., June 1, 2009; 7(6): 787 - 798. [Abstract] [Full Text] [PDF]

				M. A. Lafleur, D. Xu, and M. E. Hemler Tetraspanin Proteins Regulate Membrane Type-1 Matrix Metalloproteinase-dependent Pericellular Proteolysis Mol. Biol. Cell, April 1, 2009; 20(7): 2030 - 2040. [Abstract] [Full Text] [PDF]

				G. Baldwin, V. Novitskaya, R. Sadej, E. Pochec, A. Litynska, C. Hartmann, J. Williams, L. Ashman, J. A. Eble, and F. Berditchevski Tetraspanin CD151 Regulates Glycosylation of {alpha}3{beta}1 Integrin J. Biol. Chem., December 19, 2008; 283(51): 35445 - 35454. [Abstract] [Full Text] [PDF]

				C.-W. Chien, S.-C. Lin, Y.-Y. Lai, B.-W. Lin, S.-C. Lin, J.-C. Lee, and S.-J. Tsai Regulation of CD151 by Hypoxia Controls Cell Adhesion and Metastasis in Colorectal Cancer Clin. Cancer Res., December 15, 2008; 14(24): 8043 - 8051. [Abstract] [Full Text] [PDF]

				U. Dutta and L. M. Shaw A Key Tyrosine (Y1494) in the {beta}4 Integrin Regulates Multiple Signaling Pathways Important for Tumor Development and Progression Cancer Res., November 1, 2008; 68(21): 8779 - 8787. [Abstract] [Full Text] [PDF]

				E. Shema, I. Tirosh, Y. Aylon, J. Huang, C. Ye, N. Moskovits, N. Raver-Shapira, N. Minsky, J. Pirngruber, G. Tarcic, et al. The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor suppressor through selective regulation of gene expression Genes & Dev., October 1, 2008; 22(19): 2664 - 2676. [Abstract] [Full Text] [PDF]