This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend 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 Goldberg, G. S. Articles by Tsuda, H. Search for Related Content PubMed PubMed Citation Articles by Goldberg, G. S. Articles by Tsuda, H.

Global Effects of Anchorage on Gene Expression during Mammary Carcinoma Cell Growth Reveal Role of Tumor Necrosis Factor-related Apoptosis-inducing Ligand in Anoikis¹

Experimental Pathology and Chemotherapy Division [G. S. G., A. N., H. T.] and Cancer Genomics Division [H. I., M. O.], National Cancer Center Research Institute, Tokyo 104, Japan; Laboratory of Molecular Oncology and Cell Cycle Regulation, Howard Hughes Medical Institute, Departments of Medicine, Genetics, and Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 [Z. J., W. S. E-D.]; and Biological Sciences, State University of New York, Buffalo, New York 14260 [G. S. G.]

Anchorage-independent growth is a hallmark of tumor cells. We compared gene expression profiles of anchored and nonanchored human mammary carcinoma cells to study this phenomenon. In this study, we show that anchorage had striking effects on cell growth and morphology but altered transcript levels from a limited number of genes. Only about 1% of mRNA transcripts detected in these cells was altered by anchorage. These include genes related to amino acid and polyamine metabolism, apoptosis, ion channels, cytoskeletal and stress proteins, transcription factors, and growth factors. Some of these may be crucial for the survival of transformed cells. For example, clusterin and the tumor necrosis factor-related apoptosis inducing ligand (TRAIL) were suppressed by anchorage, which could help prevent programmed cell death of these tumor cells. In addition to suppressing TRAIL expression, anchorage also decreased the susceptibility of these tumor cells to TRAIL-induced apoptosis as determined by poly(ADP-ribose) phosphorylase cleavage, annexin-V binding (P < 0.01), and cell cycle analysis (P < 0.0001). These data may help explain mechanisms by which anchorage prevents apoptosis of cells that would otherwise experience anoikis. Thus, genes found to be altered by this analysis could serve as potential targets for anticancer therapy. These findings suggest that TRAIL may be used as a means to target circulating epithelial tumor cells before their attachment and colonization at new sites.

This article has been cited by other articles:

				R. Izmailyan and W. Chang Vaccinia Virus WR53.5/F14.5 Protein Is a New Component of Intracellular Mature Virus and Is Important for Calcium-Independent Cell Adhesion and Vaccinia Virus Virulence in Mice J. Virol., October 15, 2008; 82(20): 10079 - 10087. [Abstract] [Full Text] [PDF]

				A. Grosse-Wilde and C. J. Kemp Metastasis Suppressor Function of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-R in Mice: Implications for TRAIL-Based Therapy in Humans? Cancer Res., August 1, 2008; 68(15): 6035 - 6037. [Abstract] [Full Text] [PDF]

				L. M. Laguinge, R. N. Samara, W. Wang, W. S. El-Deiry, G. Corner, L. Augenlicht, L. Mishra, and J. M. Jessup DR5 Receptor Mediates Anoikis in Human Colorectal Carcinoma Cell Lines Cancer Res., February 1, 2008; 68(3): 909 - 917. [Abstract] [Full Text] [PDF]

				R. N. Samara, L. M. Laguinge, and J. M. Jessup Carcinoembryonic Antigen Inhibits Anoikis in Colorectal Carcinoma Cells by Interfering with Trail-R2 (DR5) Signaling Cancer Res., May 15, 2007; 67(10): 4774 - 4782. [Abstract] [Full Text] [PDF]

				P. Patwardhan, Y. Shen, G. S. Goldberg, and W. T. Miller Individual Cas Phosphorylation Sites Are Dispensable for Processive Phosphorylation by Src and Anchorage-independent Cell Growth J. Biol. Chem., July 28, 2006; 281(30): 20689 - 20697. [Abstract] [Full Text] [PDF]

				Y. Shen, Z. Jia, R. G. Nagele, H. Ichikawa, and G. S. Goldberg Src Uses Cas to Suppress Fhl1 in Order to Promote Nonanchored Growth and Migration of Tumor Cells Cancer Res., February 1, 2006; 66(3): 1543 - 1552. [Abstract] [Full Text] [PDF]

				R. S. Hauptschein, K. E. Sloan, C. Torella, R. Moezzifard, M. Giel-Moloney, C. Zehetmeier, C. Unger, L. L. Ilag, and D. G. Jay Functional Proteomic Screen Identifies a Modulating Role for CD44 in Death Receptor-Mediated Apoptosis Cancer Res., March 1, 2005; 65(5): 1887 - 1896. [Abstract] [Full Text] [PDF]

				D. B. Alexander, H. Ichikawa, J. F. Bechberger, V. Valiunas, M. Ohki, C. C. G. Naus, T. Kunimoto, H. Tsuda, W. T. Miller, and G. S. Goldberg Normal Cells Control the Growth of Neighboring Transformed Cells Independent of Gap Junctional Communication and Src Activity Cancer Res., February 15, 2004; 64(4): 1347 - 1358. [Abstract] [Full Text] [PDF]

				G. S. Goldberg, D. B. Alexander, P. Pellicena, Z.-Y. Zhang, H. Tsuda, and W. T. Miller Src Phosphorylates Cas on Tyrosine 253 to Promote Migration of Transformed Cells J. Biol. Chem., November 21, 2003; 278(47): 46533 - 46540. [Abstract] [Full Text] [PDF]

				M. S. Shin, H. S. Kim, S. H. Lee, W. S. Park, S. Y. Kim, J. Y. Park, J. H. Lee, S. K. Lee, S. N. Lee, S. S. Jung, et al. Mutations of Tumor Necrosis Factor-related Apoptosis-inducing Ligand Receptor 1 (TRAIL-R1) and Receptor 2 (TRAIL-R2) Genes in Metastatic Breast Cancers Cancer Res., July 1, 2001; 61(13): 4942 - 4946. [Abstract] [Full Text] [PDF]