Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

J. Cell Biol. 171 (3): 559-568

Copyright © 2005 by the Rockefeller University Press.

Article

The matrix protein CCN1 (CYR61) induces apoptosis in fibroblasts

Viktor Todorovicç, Chih-Chiun Chen, Nissim Hay, , and Lester F. Lau

Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago College of Medicine, Chicago, IL 60607

Correspondence to Lester F. Lau: LFLau{at}uic.edu

Abstract: Integrin-mediated cell adhesion to extracellular matrix proteins is known to promote cell survival, whereas detachment from the matrix can cause rapid apoptotic death in some cell types. Contrary to this paradigm, we show that fibroblast adhesion to the angiogenic matrix protein CCN1 (CYR61) induces apoptosis, whereas endothelial cell adhesion to CCN1 promotes cell survival. CCN1 induces fibroblast apoptosis through its adhesion receptors, integrin {alpha}6ß1 and the heparan sulfate proteoglycan (HSPG) syndecan-4, triggering the transcription-independent p53 activation of Bax to render cytochrome c release and activation of caspase-9 and -3. Neither caspase-8 activity nor de novo transcription or translation is required for this process. These results show that cellular interaction with a specific matrix protein can either induce or suppress apoptosis in a cell type–specific manner and that integrin {alpha}6ß1-HSPGs can function as receptors to induce p53-dependent apoptosis.

Abbreviations used in this paper: DRB, 5,6-dichloro-1-ß-D-ribofuranosylbenzimidazole; FN, fibronectin; HSF, human skin fibroblast; HSPG, heparan sulfate proteoglycan; HUVEC, human umbilical vein endothelial cell; JNK, c-Jun NH2-terminal kinase; LN, laminin; MEF, mouse embryonic fibroblast; PLL, poly-L-lysine; VN, vitronectin.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
An EMILIN1-Negative Microenvironment Promotes Tumor Cell Proliferation and Lymph Node Invasion.
C. Danussi, A. Petrucco, B. Wassermann, T. M. E. Modica, E. Pivetta, L. D. B. Belluz, A. Colombatti, and P. Spessotto (2012)
Cancer Prevention Research 5, 1131-1143
   Abstract »    Full Text »    PDF »
Matricellular Proteins in Cardiac Adaptation and Disease.
N. G. Frangogiannis (2012)
Physiol Rev 92, 635-688
   Abstract »    Full Text »    PDF »
Matricellular Protein CCN1 Activates a Proinflammatory Genetic Program in Murine Macrophages.
T. Bai, C.-C. Chen, and L. F. Lau (2010)
J. Immunol. 184, 3223-3232
   Abstract »    Full Text »    PDF »
Effects of reduced frequency of milk removal on gene expression in the bovine mammary gland.
M. D. Littlejohn, C. G. Walker, H. E. Ward, K. B. Lehnert, R. G. Snell, G. A. Verkerk, R. J. Spelman, D. A. Clark, and S. R. Davis (2010)
Physiol Genomics 41, 21-32
   Abstract »    Full Text »    PDF »
Silencing cAMP-response Element-binding Protein (CREB) Identifies CYR61 as a Tumor Suppressor Gene in Melanoma.
A. S. Dobroff, H. Wang, V. O. Melnikova, G. J. Villares, M. Zigler, L. Huang, and M. Bar-Eli (2009)
J. Biol. Chem. 284, 26194-26206
   Abstract »    Full Text »    PDF »
Matrix Protein CCN1 Is Critical for Prostate Carcinoma Cell Proliferation and TRAIL-Induced Apoptosis.
C. A. Franzen, C.-C. Chen, V. Todorovic, V. Juric, R. I. Monzon, and L. F. Lau (2009)
Mol. Cancer Res. 7, 1045-1055
   Abstract »    Full Text »    PDF »
Fas-Mediated Apoptosis Is Regulated by the Extracellular Matrix Protein CCN1 (CYR61) In Vitro and In Vivo.
V. Juric, C.-C. Chen, and L. F. Lau (2009)
Mol. Cell. Biol. 29, 3266-3279
   Abstract »    Full Text »    PDF »
Cysteine-Rich Protein 61 and Connective Tissue Growth Factor Induce Deadhesion and Anoikis of Retinal Pericytes.
H. Liu, R. Yang, B. Tinner, A. Choudhry, N. Schutze, and B. Chaqour (2008)
Endocrinology 149, 1666-1677
   Abstract »    Full Text »    PDF »
Regulation of the Extrinsic Apoptotic Pathway by the Extracellular Matrix Glycoprotein EMILIN2.
M. Mongiat, G. Ligresti, S. Marastoni, E. Lorenzon, R. Doliana, and A. Colombatti (2007)
Mol. Cell. Biol. 27, 7176-7187
   Abstract »    Full Text »    PDF »
Nephroblastoma Overexpressed/Cysteine-Rich Protein 61/Connective Tissue Growth Factor/Nephroblastoma Overexpressed Gene-3 (NOV/CCN3), a Selective Adrenocortical Cell Proapoptotic Factor, Is Down-Regulated in Childhood Adrenocortical Tumors.
M. Doghman, M. Arhatte, H. Thibout, G. Rodrigues, J. De Moura, S. Grosso, A. N. West, M. Laurent, J.-C. Mas, A. Bongain, et al. (2007)
J. Clin. Endocrinol. Metab. 92, 3253-3260
   Abstract »    Full Text »    PDF »
All in the CCN family: essential matricellular signaling modulators emerge from the bunker.
A. Leask and D. J. Abraham (2006)
J. Cell Sci. 119, 4803-4810
   Abstract »    Full Text »    PDF »
CCN3 controls 3D spatial localization of melanocytes in the human skin through DDR1.
M. Fukunaga-Kalabis, G. Martinez, Z.-J. Liu, J. Kalabis, P. Mrass, W. Weninger, S. M. Firth, N. Planque, B. Perbal, and M. Herlyn (2006)
J. Cell Biol. 175, 563-569
   Abstract »    Full Text »    PDF »
The Matricellular Protein CCN1 Is Essential for Cardiac Development.
F.-E Mo and L. F. Lau (2006)
Circ. Res. 99, 961-969
   Abstract »    Full Text »    PDF »
Testicular Gene Expression Profiling following Prepubertal Rat Mono-(2-ethylhexyl) Phthalate Exposure Suggests a Common Initial Genetic Response at Fetal and Prepubertal Ages.
S. A. Lahousse, D. G. Wallace, D. Liu, K. W. Gaido, and K. J. Johnson (2006)
Toxicol. Sci. 93, 369-381
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882