Article

Apoptosis of adherent cells by recruitment of caspase-8 to unligated integrins

Dwayne G. Stupack, Xose S. Puente, Souphaphone Boutsaboualoy, Chris M. Storgard, and David A. Cheresh

Department of Immunology and Department of Vascular Biology, The Scripps Research Institute, La Jolla, CA 92037

Address correspondence to David Cheresh, The Scripps Research Institute, Department of Immunology, IMM24 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Tel.: (858) 784-8281. Fax: (858) 784-8926. E-mail: cheresh{at}scripps.edu

Abstract: Integrin-mediated adhesion promotes cell survival in vitro, whereas integrin antagonists induce apoptosis of adherent cells in vivo. Here, we demonstrate that cells adherent within a three-dimensional extracellular matrix undergo apoptosis due to expression of unligated integrins, the ß subunit cytoplasmic domain, or its membrane proximal sequence KLLITIHDRKEF. Integrin-mediated death requires initiator, but not stress, caspase activity and is distinct from anoikis, which is caused by the loss of adhesion per se. Surprisingly, unligated integrin or ß integrin tails recruit caspase-8 to the membrane, where it becomes activated in a death receptor–independent manner. Integrin ligation disrupts this integrin–caspase containing complex and increases survival, revealing an unexpected role for integrins in the regulation of apoptosis and tissue remodeling.

Key Words: cell adhesion; apoptosis; caspase; integrin; ligands

{beta}-1,4-Galactosyltransferase III Enhances Invasive Phenotypes Via {beta}1-Integrin and Predicts Poor Prognosis in Neuroblastoma.

H.-H. Chang, C.-H. Chen, C.-H. Chou, Y.-F. Liao, M.-J. Huang, Y.-H. Chen, W.-J. Wang, J. Huang, J.-S. Hung, W.-L. Ho, et al. (2013)
Clin. Cancer Res. 19, 1705-1716
 |  Abstract »  |  Full Text »  |  PDF »

Dependence receptor TrkC is a putative colon cancer tumor suppressor.

A.-L. Genevois, G. Ichim, M.-M. Coissieux, M.-P. Lambert, F. Lavial, D. Goldschneider, L. Jarrosson-Wuilleme, F. Lepinasse, G. Gouysse, Z. Herceg, et al. (2013)
PNAS 110, 3017-3022
 |  Abstract »  |  Full Text »  |  PDF »

Insulin-like Growth Factor (IGF) Signaling Requires {alpha}v{beta}3-IGF1-IGF Type 1 Receptor (IGF1R) Ternary Complex Formation in Anchorage Independence, and the Complex Formation Does Not Require IGF1R and Src Activation.

M. Fujita, Y. K. Takada, and Y. Takada (2013)
J. Biol. Chem. 288, 3059-3069
 |  Abstract »  |  Full Text »  |  PDF »

Encapsulation of factor IX-engineered mesenchymal stem cells in fibrinogen-alginate microcapsules enhances their viability and transgene secretion.

B. Sayyar, M. Dodd, J. Wen, S. Ma, L. Marquez-Curtis, A. Janowska-Wieczorek, and G. Hortelano (2012)
Journal of Tissue Engineering 3, 2041731412462018
 |  Abstract »  |  Full Text »  |  PDF »

PINCH-1 promotes Bcl-2-dependent survival signalling and inhibits JNK-mediated apoptosis in the primitive endoderm.

E. Montanez, E. Karakose, D. Tischner, A. Villunger, and R. Fassler (2012)
J. Cell Sci. 125, 5233-5240
 |  Abstract »  |  Full Text »  |  PDF »

The Abluminal Endothelial Membrane in Neurovascular Remodeling in Health and Disease.

D. M. Hermann and A. ElAli (2012)
Science Signaling 5, re4
 |  Abstract »  |  Full Text »  |  PDF »

FAS1 Domain Protein Inhibits VEGF165-Induced Angiogenesis by Targeting the Interaction between VEGFR-2 and {alpha}v{beta}3 Integrin.

J.-O. Nam, H.-N. Son, E. Jun, K. Cha, B.-H. Lee, R.-W. Park, and I.-S. Kim (2012)
Mol. Cancer Res. 10, 1010-1020
 |  Abstract »  |  Full Text »  |  PDF »

Pivotal role of RanBP9 in integrin-dependent focal adhesion signaling and assembly.

J. A. Woo, S.-E. Roh, M. K. Lakshmana, and D. E. Kang (2012)
FASEB J 26, 1672-1681
 |  Abstract »  |  Full Text »  |  PDF »

Overcoming anoikis - pathways to anchorage-independent growth in cancer.

M. C. Guadamillas, A. Cerezo, and M. A. del Pozo (2011)
J. Cell Sci. 124, 3189-3197
 |  Abstract »  |  Full Text »  |  PDF »

Pharmacoproteomic Analysis of a Novel Cell-permeable Peptide Inhibitor of Tumor-induced Angiogenesis.

J.-Y. Bang, E.-Y. Kim, D.-K. Kang, S.-I. Chang, M.-H. Han, K.-H. Baek, and I.-C. Kang (2011)
Mol. Cell. Proteomics 10, M110.005264
 |  Abstract »  |  Full Text »  |  PDF »

Targeting Cell Spreading: A Method of Sensitizing Metastatic Tumor Cells to TRAIL-Induced Apoptosis.

L. E. Phipps, S. Hino, and R. J. Muschel (2011)
Mol. Cancer Res. 9, 249-258
 |  Abstract »  |  Full Text »  |  PDF »

Identification of Subtilase Cytotoxin (SubAB) Receptors Whose Signaling, in Association with SubAB-Induced BiP Cleavage, Is Responsible for Apoptosis in HeLa Cells.

K. Yahiro, M. Satoh, N. Morinaga, H. Tsutsuki, K. Ogura, S. Nagasawa, F. Nomura, J. Moss, and M. Noda (2011)
Infect. Immun. 79, 617-627
 |  Abstract »  |  Full Text »  |  PDF »

Dependence Receptors: From Basic Research to Drug Development.

P. Mehlen and D. E. Bredesen (2011)
Science Signaling 4, mr2
 |  Abstract »  |  Full Text »  |  PDF »

Phase I Study of E7820, an Oral Inhibitor of Integrin {alpha}-2 Expression with Antiangiogenic Properties, in Patients with Advanced Malignancies.

M. Mita, K. R. Kelly, A. Mita, A. D. Ricart, O. Romero, A. Tolcher, L. Hook, C. Okereke, I. Krivelevich, D. P. Rossignol, et al. (2011)
Clin. Cancer Res. 17, 193-200
 |  Abstract »  |  Full Text »  |  PDF »

Focal adhesions in osteoneogenesis.

M. J. P. Biggs and M. J. Dalby (2010)
Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine 224, 1441-1453
 |  Abstract »  |  PDF »

Characterization of integrin engagement during defined human embryonic stem cell culture.

Y. Meng, S. Eshghi, Y. J. Li, R. Schmidt, D. V. Schaffer, and K. E. Healy (2010)
FASEB J 24, 1056-1065
 |  Abstract »  |  Full Text »  |  PDF »

Rab5 Mediates Caspase-8-promoted Cell Motility and Metastasis.

V. A. Torres, A. Mielgo, S. Barbero, R. Hsiao, J. A. Wilkins, and D. G. Stupack (2010)
Mol. Biol. Cell 21, 369-376
 |  Abstract »  |  Full Text »  |  PDF »

Parsing the niche code: the molecular mechanisms governing hematopoietic stem cell adhesion and differentiation.

E. C. Forsberg and S. Smith-Berdan (2009)
Haematologica 94, 1477-1481
 |  Full Text »  |  PDF »

Caspase-8 Association with the Focal Adhesion Complex Promotes Tumor Cell Migration and Metastasis.

S. Barbero, A. Mielgo, V. Torres, T. Teitz, D. J. Shields, D. Mikolon, M. Bogyo, D. Barila, J. M. Lahti, D. Schlaepfer, et al. (2009)
Cancer Res. 69, 3755-3763
 |  Abstract »  |  Full Text »  |  PDF »

Netrin-1 acts as a survival factor for aggressive neuroblastoma.

C. Delloye-Bourgeois, J. Fitamant, A. Paradisi, D. Cappellen, S. Douc-Rasy, M.-A. Raquin, D. Stupack, A. Nakagawara, R. Rousseau, V. Combaret, et al. (2009)
J. Exp. Med. 206, 833-847
 |  Abstract »  |  Full Text »  |  PDF »

Syndecan-1 regulates {alpha}v{beta}3 and {alpha}v{beta}5 integrin activation during angiogenesis and is blocked by synstatin, a novel peptide inhibitor.

D. M. Beauvais, B. J. Ell, A. R. McWhorter, and A. C. Rapraeger (2009)
J. Exp. Med. 206, 691-705
 |  Abstract »  |  Full Text »  |  PDF »

To Die or Not to Die, That's the Question--And the Answer May Depend on Netrin-1.

M. P. Schon and M. Schon (2009)
J Natl Cancer Inst 101, 217-219
 |  Full Text »  |  PDF »

Proapoptotic Function of Integrin {beta}3 in Human Hepatocellular Carcinoma Cells.

Y. Wu, J. Zuo, G. Ji, H. Saiyin, X. Liu, F. Yin, N. Cao, Y. Wen, J. J. Li, and L. Yu (2009)
Clin. Cancer Res. 15, 60-69
 |  Abstract »  |  Full Text »  |  PDF »

Integrin-associated Lyn Kinase Promotes Cell Survival by Suppressing Acid Sphingomyelinase Activity.

D. A. Chudakova, Y. H. Zeidan, B. W. Wheeler, J. Yu, S. A. Novgorodov, M. S. Kindy, Y. A. Hannun, and T. I. Gudz (2008)
J. Biol. Chem. 283, 28806-28816
 |  Abstract »  |  Full Text »  |  PDF »

Integrins: The Keys to Unlocking Angiogenesis.

R. Silva, G. D'Amico, K. M. Hodivala-Dilke, and L. E. Reynolds (2008)
Arterioscler Thromb Vasc Biol 28, 1703-1713
 |  Abstract »  |  Full Text »  |  PDF »

Regulation of cell survival by Na+/H+ exchanger-1.

J. R. Schelling and B. G. Abu Jawdeh (2008)
Am J Physiol Renal Physiol 295, F625-F632
 |  Abstract »  |  Full Text »  |  PDF »

Anti-integrin monoclonal antibody CNTO 95 enhances the therapeutic efficacy of fractionated radiation therapy in vivo.

S. Ning, J. A. Nemeth, R. L. Hanson, K. Forsythe, and S. J. Knox (2008)
Mol. Cancer Ther. 7, 1569-1578
 |  Abstract »  |  Full Text »  |  PDF »

Identification of a Critical Tyrosine Residue in Caspase 8 That Promotes Cell Migration.

S. Barbero, D. Barila, A. Mielgo, V. Stagni, K. Clair, and D. Stupack (2008)
J. Biol. Chem. 283, 13031-13034
 |  Abstract »  |  Full Text »  |  PDF »

Targeted imaging of hypoxia-induced integrin activation in myocardium early after infarction.

L. Kalinowski, L. W. Dobrucki, D. F. Meoli, D. P. Dione, M. M. Sadeghi, J. A. Madri, and A. J. Sinusas (2008)
J Appl Physiol 104, 1504-1512
 |  Abstract »  |  Full Text »  |  PDF »

Role of JNK in network formation of human lung microvascular endothelial cells.

M. Medhora, A. Dhanasekaran, P. F. Pratt Jr., C. R. Cook, L. K. Dunn, S. K. Gruenloh, and E. R. Jacobs (2008)
Am J Physiol Lung Cell Mol Physiol 294, L676-L685
 |  Abstract »  |  Full Text »  |  PDF »

Activated Mast Cells Induce Endothelial Cell Apoptosis by a Combined Action of Chymase and Tumor Necrosis Factor-{alpha}.

H. M. Heikkila, S. Latti, M. J. Leskinen, J. K. Hakala, P. T. Kovanen, and K. A. Lindstedt (2008)
Arterioscler Thromb Vasc Biol 28, 309-314
 |  Abstract »  |  Full Text »  |  PDF »

Apoptosis in Microencapsulated Juvenile Rabbit Chondrocytes Induced by Ofloxacin: Role Played by beta1-Integrin Receptor.

Z.-g. Sheng, S. Peng, C.-y. Wang, H.-b. Li, R. K. Hajela, Y.-e. Wang, Q.-q. Li, M.-f. Liu, Y.-s. Dong, and G. Han (2007)
J. Pharmacol. Exp. Ther. 322, 155-165
 |  Abstract »  |  Full Text »  |  PDF »

Base Excision Repair Proteins Are Required for Integrin-Mediated Suppression of Bleomycin-Induced DNA Breakage in Murine Lung Endothelial Cells.

J. L. Rose, K. C. Reeves, R. I. Likhotvorik, and D. G. Hoyt (2007)
J. Pharmacol. Exp. Ther. 321, 318-326
 |  Abstract »  |  Full Text »  |  PDF »

Cooperation between VEGF and {beta}3 integrin during cardiac vascular development.

S. M. Weis, J. N. Lindquist, L. A. Barnes, K. M. Lutu-Fuga, J. Cui, M. R. Wood, and D. A. Cheresh (2007)
Blood 109, 1962-1970
 |  Abstract »  |  Full Text »  |  PDF »

Disruption of {alpha}-actinin-integrin interactions at focal adhesions renders osteoblasts susceptible to apoptosis.

J. W. Triplett and F. M. Pavalko (2006)
Am J Physiol Cell Physiol 291, C909-C921
 |  Abstract »  |  Full Text »  |  PDF »

Blockade of {alpha}vbeta3 and {alpha}vbeta5 integrins by RGD mimetics induces anoikis and not integrin-mediated death in human endothelial cells.

S. Maubant, D. Saint-Dizier, M. Boutillon, F. Perron-Sierra, P. J. Casara, J. A. Hickman, G. C. Tucker, and E. Van Obberghen-Schilling (2006)
Blood 108, 3035-3044
 |  Abstract »  |  Full Text »  |  PDF »

Galectin-1: biphasic growth regulation of Leydig tumor cells.

V. A. Biron, M. M. Iglesias, M. F. Troncoso, M. Besio-Moreno, Z. J. Patrignani, O. P. Pignataro, and C. Wolfenstein-Todel (2006)
Glycobiology 16, 810-821
 |  Abstract »  |  Full Text »  |  PDF »

Anaplastic Lymphoma Kinase Is a Dependence Receptor Whose Proapoptotic Functions Are Activated by Caspase Cleavage.

J. Mourali, A. Benard, F. C. Lourenco, C. Monnet, C. Greenland, C. Moog-Lutz, C. Racaud-Sultan, D. Gonzalez-Dunia, M. Vigny, P. Mehlen, et al. (2006)
Mol. Cell. Biol. 26, 6209-6222
 |  Abstract »  |  Full Text »  |  PDF »

Metastasis Suppressor Proteins: Discovery, Molecular Mechanisms, and Clinical Application..

C. W. Rinker-Schaeffer, J. P. O'Keefe, D. R. Welch, and D. Theodorescu (2006)
Clin. Cancer Res. 12, 3882-3889
 |  Full Text »  |  PDF »

Does Integrin-Mediated Cell Death Confer Tissue Tropism in Metastasis?.

J. M. Lahti, T. Teitz, and D. G. Stupack (2006)
Cancer Res. 66, 5981-5984
 |  Abstract »  |  Full Text »  |  PDF »

The matrix protein CCN1 (CYR61) induces apoptosis in fibroblasts.

V. Todorovicc, C.-C. Chen, N. Hay, and L. F. Lau (2005)
J. Cell Biol. 171, 559-568
 |  Abstract »  |  Full Text »  |  PDF »

Hypoxia of endothelial cells leads to MMP-2-dependent survival and death.

Y. Ben-Yosef, A. Miller, S. Shapiro, and N. Lahat (2005)
Am J Physiol Cell Physiol 289, C1321-C1331
 |  Abstract »  |  Full Text »  |  PDF »

Endothelial apoptosis induced by inhibition of integrins {alpha}v{beta}3 and {alpha}v{beta}5 involves ceramide metabolic pathways.

A. Erdreich-Epstein, L. B. Tran, O. T. Cox, E. Y. Huang, W. E. Laug, H. Shimada, and M. Millard (2005)
Blood 105, 4353-4361
 |  Abstract »  |  Full Text »  |  PDF »

Canstatin Acts on Endothelial and Tumor Cells via Mitochondrial Damage Initiated through Interaction with {alpha}v{beta}3 and {alpha}v{beta}5 Integrins.

C. Magnon, A. Galaup, B. Mullan, V. Rouffiac, J.-M. Bidart, F. Griscelli, P. Opolon, and M. Perricaudet (2005)
Cancer Res. 65, 4353-4361
 |  Abstract »  |  Full Text »  |  PDF »

The Hydra Phenomenon of Cancer: Why Tumors Recur Locally after Microscopically Complete Resection.

M. Hockel and N. Dornhofer (2005)
Cancer Res. 65, 2997-3002
 |  Abstract »  |  Full Text »  |  PDF »

Src Kinase Activity Is Required for Integrin {alpha}V{beta}3-Mediated Activation of Nuclear Factor-{kappa}B.

D. L. Courter, L. Lomas, M. Scatena, and C. M. Giachelli (2005)
J. Biol. Chem. 280, 12145-12151
 |  Abstract »  |  Full Text »  |  PDF »

Gingipains from Porphyromonas gingivalis W83 Induce Cell Adhesion Molecule Cleavage and Apoptosis in Endothelial Cells.

S. M. Sheets, J. Potempa, J. Travis, C. A. Casiano, and H. M. Fletcher (2005)
Infect. Immun. 73, 1543-1552
 |  Abstract »  |  Full Text »  |  PDF »

Unoccupied {alpha}v{beta}3 Integrin Regulates Osteoclast Apoptosis by Transmitting a Positive Death Signal.

H. Zhao, F. P. Ross, and S. L. Teitelbaum (2005)
Mol. Endocrinol. 19, 771-780
 |  Abstract »  |  Full Text »  |  PDF »

Genes Regulated in Neurons Undergoing Transcription-dependent Apoptosis Belong to Signaling Pathways Rather than the Apoptotic Machinery.

S. Desagher, D. Severac, A. Lipkin, C. Bernis, W. Ritchie, A. Le Digarcher, and L. Journot (2005)
J. Biol. Chem. 280, 5693-5702
 |  Abstract »  |  Full Text »  |  PDF »

Combinatorial antibody libraries from cancer patients yield ligand-mimetic Arg-Gly-Asp-containing immunoglobulins that inhibit breast cancer metastasis.

B. Felding-Habermann, R. A. Lerner, A. Lillo, S. Zhuang, M. R. Weber, S. Arrues, C. Gao, S. Mao, A. Saven, and K. D. Janda (2004)
PNAS 101, 17210-17215
 |  Abstract »  |  Full Text »  |  PDF »

Elevated Flk1 (Vascular Endothelial Growth Factor Receptor 2) Signaling Mediates Enhanced Angiogenesis in {beta}3-Integrin-Deficient Mice.

A. R. Reynolds, L. E. Reynolds, T. E. Nagel, J. C. Lively, S. D. Robinson, D. J. Hicklin, S. C. Bodary, and K. M. Hodivala-Dilke (2004)
Cancer Res. 64, 8643-8650
 |  Abstract »  |  Full Text »  |  PDF »

Integrin {alpha}v-mediated inactivation of p53 controls a MEK1-dependent melanoma cell survival pathway in three-dimensional collagen.

W. Bao and S. Stromblad (2004)
J. Cell Biol. 167, 745-756
 |  Abstract »  |  Full Text »  |  PDF »

FLICE/caspase-8 activation triggers anoikis induced by {beta}1-integrin blockade in human keratinocytes.

A. Marconi, P. Atzei, C. Panza, C. Fila, R. Tiberio, F. Truzzi, T. Wachter, M. Leverkus, and C. Pincelli (2004)
J. Cell Sci. 117, 5815-5823
 |  Abstract »  |  Full Text »  |  PDF »

The syndecan-1 ectodomain regulates {alpha}v{beta}3 integrin activity in human mammary carcinoma cells.

D. M. Beauvais, B. J. Burbach, and A. C. Rapraeger (2004)
J. Cell Biol. 167, 171-181
 |  Abstract »  |  Full Text »  |  PDF »

Role of the Dependence Receptor DCC in Colorectal Cancer Pathogenesis.

P. Mehlen and E. R. Fearon (2004)
J. Clin. Oncol. 22, 3420-3428
 |  Abstract »  |  Full Text »  |  PDF »

Switch from {alpha}v{beta}5 to {alpha}v{beta}6 integrin expression protects squamous cell carcinomas from anoikis.

S. M. Janes and F. M. Watt (2004)
J. Cell Biol. 166, 419-431
 |  Abstract »  |  Full Text »  |  PDF »

Extracellular Matrix Protects Pancreatic {beta}-Cells Against Apoptosis: Role of Short- and Long-Term Signaling Pathways.

E. Hammar, G. Parnaud, D. Bosco, N. Perriraz, K. Maedler, M. Donath, D. G. Rouiller, and P. A. Halban (2004)
Diabetes 53, 2034-2041
 |  Abstract »  |  Full Text »  |  PDF »

Translocation of Full-length Bid to Mitochondria during Anoikis.

A. J. Valentijn and A. P. Gilmore (2004)
J. Biol. Chem. 279, 32848-32857
 |  Abstract »  |  Full Text »  |  PDF »

Antiangiogenic and Antitumoral Activity of Phenyl-3-(2-Chloroethyl)Ureas: A Class of Soft Alkylating Agents Disrupting Microtubules That Are Unaffected by Cell Adhesion-Mediated Drug Resistance.

E. Petitclerc, R. G. Deschesnes, M.-F. Cote, C. Marquis, R. Janvier, J. Lacroix, E. Miot-Noirault, J. Legault, E. Mounetou, J.-C. Madelmont, et al. (2004)
Cancer Res. 64, 4654-4663
 |  Abstract »  |  Full Text »  |  PDF »

RGDS peptide induces caspase 8 and caspase 9 activation in human endothelial cells.

M. S. Aguzzi, C. Giampietri, F. De Marchis, F. Padula, R. Gaeta, G. Ragone, M. C. Capogrossi, and A. Facchiano (2004)
Blood 103, 4180-4187
 |  Abstract »  |  Full Text »  |  PDF »

Integrin {beta}3 Overexpression Suppresses Tumor Growth in a Human Model of Gliomagenesis: Implications for the Role of {beta}3 Overexpression in Glioblastoma Multiforme.

M. Kanamori, S. R. V. Berg, G. Bergers, M. S. Berger, and R. O. Pieper (2004)
Cancer Res. 64, 2751-2758
 |  Abstract »  |  Full Text »  |  PDF »

Apoptosis and Dependence Receptors: A Molecular Basis for Cellular Addiction.

D. E. BREDESEN, P. MEHLEN, and S. RABIZADEH (2004)
Physiol Rev 84, 411-430
 |  Abstract »  |  Full Text »  |  PDF »

{beta}3-Integrin Mediates Smooth Muscle Cell Accumulation in Neointima After Carotid Ligation in Mice.

E. T. Choi, M. F. Khan, J. E. Leidenfrost, E. T. Collins, K. P. Boc, B. R. Villa, D. V. Novack, W. C. Parks, and D. R. Abendschein (2004)
Circulation 109, 1564-1569
 |  Abstract »  |  Full Text »  |  PDF »

The Homeobox Transcription Factor Hox D3 Promotes Integrin {alpha}5{beta}1 Expression and Function during Angiogenesis.

N. J. Boudreau and J. A. Varner (2004)
J. Biol. Chem. 279, 4862-4868
 |  Abstract »  |  Full Text »  |  PDF »

Extracellular matrix regulates glomerular epithelial cell survival and proliferation.

K. Bijian, T. Takano, J. Papillon, A. Khadir, and A. V. Cybulsky (2004)
Am J Physiol Renal Physiol 286, F255-F266
 |  Abstract »  |  Full Text »  |  PDF »

The Akt-regulated Forkhead Transcription Factor FOXO3a Controls Endothelial Cell Viability through Modulation of the Caspase-8 Inhibitor FLIP.

C. Skurk, H. Maatz, H.-S. Kim, J. Yang, M. R. Abid, W. C. Aird, and K. Walsh (2004)
J. Biol. Chem. 279, 1513-1525
 |  Abstract »  |  Full Text »  |  PDF »

CD29 and CD7 Mediate Galectin-3-Induced Type II T-Cell Apoptosis.

T. Fukumori, Y. Takenaka, T. Yoshii, H.-R. C. Kim, V. Hogan, H. Inohara, S. Kagawa, and A. Raz (2003)
Cancer Res. 63, 8302-8311
 |  Abstract »  |  Full Text »  |  PDF »

Anoikis in the Cardiovascular System: Known and Unknown Extracellular Mediators.

J.-B. Michel (2003)
Arterioscler Thromb Vasc Biol 23, 2146-2154
 |  Abstract »  |  Full Text »  |  PDF »

Endostatin Associates with Lipid Rafts and Induces Reorganization of the Actin Cytoskeleton via Down-regulation of RhoA Activity.

S. A. Wickstrom, K. Alitalo, and J. Keski-Oja (2003)
J. Biol. Chem. 278, 37895-37901
 |  Abstract »  |  Full Text »  |  PDF »

Canstatin Inhibits Akt Activation and Induces Fas-dependent Apoptosis in Endothelial Cells.

D. J. Panka and J. W. Mier (2003)
J. Biol. Chem. 278, 37632-37636
 |  Abstract »  |  Full Text »  |  PDF »

Endothelial expression of the {alpha}6{beta}4 integrin is negatively regulated during angiogenesis.

T. S. Hiran, J. E. Mazurkiewicz, P. Kreienberg, F. L. Rice, and S. E. LaFlamme (2003)
J. Cell Sci. 116, 3771-3781
 |  Abstract »  |  Full Text »  |  PDF »

Differential {alpha}v integrin-mediated Ras-ERK signaling during two pathways of angiogenesis.

J. D. Hood, R. Frausto, W. B. Kiosses, M. A. Schwartz, and D. A. Cheresh (2003)
J. Cell Biol. 162, 933-943
 |  Abstract »  |  Full Text »  |  PDF »

Caspase activation during phorbol ester-induced apoptosis requires ROCK-dependent myosin-mediated contraction.

J.-M. Lai, C.-L. Hsieh, and Z.-F. Chang (2003)
J. Cell Sci. 116, 3491-3501
 |  Abstract »  |  Full Text »  |  PDF »

Role of Raf in Vascular Protection from Distinct Apoptotic Stimuli.

A. Alavi, J. D. Hood, R. Frausto, D. G. Stupack, and D. A. Cheresh (2003)
Science 301, 94-96
 |  Abstract »  |  Full Text »  |  PDF »

Functions of Pulmonary Epithelial Integrins: From Development to Disease.

D. SHEPPARD (2003)
Physiol Rev 83, 673-686
 |  Abstract »  |  Full Text »  |  PDF »

PECAM-1 functions as a specific and potent inhibitor of mitochondrial-dependent apoptosis.

C. Gao, W. Sun, M. Christofidou-Solomidou, M. Sawada, D. K. Newman, C. Bergom, S. M. Albelda, S. Matsuyama, and P. J. Newman (2003)
Blood 102, 169-179
 |  Abstract »  |  Full Text »  |  PDF »

De Novo Expression of the Integrin {alpha}5{beta}1 Regulates {alpha}v{beta}3-mediated Adhesion and Migration on Fibrinogen.

D. P. Ly, K. M. Zazzali, and S. A. Corbett (2003)
J. Biol. Chem. 278, 21878-21885
 |  Abstract »  |  Full Text »  |  PDF »

Decrease in Survival Threshold of Quiescent Colon Carcinoma Cells in the Presence of a Small Molecule Integrin Antagonist.

M. F. Burbridge, V. Venot, P. J. Casara, F. Perron-Sierra, J. A. Hickman, and G. C. Tucker (2003)
Mol. Pharmacol. 63, 1281-1288
 |  Abstract »  |  Full Text »  |  PDF »

Early Events in the Anoikis Program Occur in the Absence of Caspase Activation.

P. Wang, A. J. Valentijn, A. P. Gilmore, and C. H. Streuli (2003)
J. Biol. Chem. 278, 19917-19925
 |  Abstract »  |  Full Text »  |  PDF »

Specific beta 1 Integrin Site Selectively Regulates Akt/Protein Kinase B Signaling via Local Activation of Protein Phosphatase 2A.

R. Pankov, E. Cukierman, K. Clark, K. Matsumoto, C. Hahn, B. Poulin, and K. M. Yamada (2003)
J. Biol. Chem. 278, 18671-18681
 |  Abstract »  |  Full Text »  |  PDF »

The Cell Adhesion Molecule CEACAM1-L Is a Substrate of Caspase-3-mediated Cleavage in Apoptotic Mouse Intestinal Cells.

C. Houde, S. Roy, N. Leung, D. W. Nicholson, and N. Beauchemin (2003)
J. Biol. Chem. 278, 16929-16935
 |  Abstract »  |  Full Text »  |  PDF »

Vascular morphogenesis: tales of two syndromes.

D. A. Marchuk, S. Srinivasan, T. L. Squire, and J. S. Zawistowski (2003)
Hum. Mol. Genet. 12, R97-112
 |  Abstract »  |  Full Text »  |  PDF »

The Mechanism of CD47-Dependent Killing of T Cells: Heterotrimeric Gi-Dependent Inhibition of Protein Kinase A.

P. P. Manna and W. A. Frazier (2003)
J. Immunol. 170, 3544-3553
 |  Abstract »  |  Full Text »  |  PDF »

Apoptotic Susceptibility of Cancer Cells Selected for Camptothecin Resistance: Gene Expression Profiling, Functional Analysis, and Molecular Interaction Mapping.

W. C. Reinhold, H. Kouros-Mehr, K. W. Kohn, A. K. Maunakea, S. Lababidi, A. Roschke, K. Stover, J. Alexander, P. Pantazis, L. Miller, et al. (2003)
Cancer Res. 63, 1000-1011
 |  Abstract »  |  Full Text »  |  PDF »

Transendothelial migration leads to protection from starvation-induced apoptosis in CD34+CD14+ circulating precursors: evidence for PECAM-1 involvement through Akt/PKB activation.

E. Ferrero, D. Belloni, P. Contini, C. Foglieni, M. E. Ferrero, M. Fabbri, A. Poggi, and M. R. Zocchi (2003)
Blood 101, 186-193
 |  Abstract »  |  Full Text »  |  PDF »

Fas Activation Induces Renal Tubular Epithelial Cell beta 8 Integrin Expression and Function in the Absence of Apoptosis.

G. Jarad, B. Wang, S. Khan, J. DeVore, H. Miao, K. Wu, S. L. Nishimura, B. A. Wible, M. Konieczkowski, J. R. Sedor, et al. (2002)
J. Biol. Chem. 277, 47826-47833
 |  Abstract »  |  Full Text »  |  PDF »

Restoration of Transforming Growth Factor {beta} Signaling by Functional Expression of Smad4 Induces Anoikis.

M. Ramachandra, I. Atencio, A. Rahman, M. Vaillancourt, A. Zou, J. Avanzini, K. Wills, R. Bookstein, and P. Shabram (2002)
Cancer Res. 62, 6045-6051
 |  Abstract »  |  Full Text »  |  PDF »

Integrin alpha V beta 3 as a target for treatment of rheumatoid arthritis and related rheumatic diseases.

R L Wilder (2002)
Ann Rheum Dis 61, ii96-99
 |  Abstract »  |  Full Text »  |  PDF »

Get a ligand, get a life: integrins, signaling and cell survival.

D. G. Stupack and D. A. Cheresh (2002)
J. Cell Sci. 115, 3729-3738
 |  Abstract »  |  Full Text »  |  PDF »

Autocrine Stimulation by Osteopontin Contributes to Antiapoptotic Signalling of Melanocytes in Dermal Collagen.

E. Geissinger, C. Weisser, P. Fischer, M. Schartl, and C. Wellbrock (2002)
Cancer Res. 62, 4820-4828
 |  Abstract »  |  Full Text »  |  PDF »

Tiny dancers: the integrin-growth factor nexus in angiogenic signaling.

S. S. Smyth and C. Patterson (2002)
J. Cell Biol. 158, 17-21
 |  Abstract »  |  Full Text »  |  PDF »

Loss of p53 Compensates for alpha v-Integrin Function in Retinal Neovascularization.

S. Stromblad, A. Fotedar, H. Brickner, C. Theesfeld, E. Aguilar de Diaz, M. Friedlander, and D. A. Cheresh (2002)
J. Biol. Chem. 277, 13371-13374
 |  Abstract »  |  Full Text »  |  PDF »

Focal Adhesions Require Catalytic Activity of Src Family Kinases To Mediate Integrin-Matrix Adhesion.

L. Li, M. Okura, and A. Imamoto (2002)
Mol. Cell. Biol. 22, 1203-1217
 |  Abstract »  |  Full Text »  |  PDF »

ECM Remodeling Regulates Angiogenesis: Endothelial Integrins Look for New Ligands.

D. G. Stupack and D. A. Cheresh (2002)
Sci. STKE 2002, pe7
 |  Abstract »  |  Full Text »  |  PDF »

The Diverse Roles of Integrins and Their Ligands in Angiogenesis.

R.O. HYNES, J.C. LIVELY, J.H. MCCARTY, D. TAVERNA, S.E. FRANCIS, K. HODIVALA-DILKE, and Q. XIAO (2002)
Cold Spring Harb Symp Quant Biol 67, 143-154
 |  Abstract »  |  PDF »

Discovery of Type IV Collagen Non-collagenous Domains as Novel Integrin Ligands and Endogenous Inhibitors of Angiogenesis.

R. KALLURI (2002)
Cold Spring Harb Symp Quant Biol 67, 255-266
 |  Abstract »  |  PDF »