The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shain, K. H.
Right arrow Articles by Dalton, W. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shain, K. H.
Right arrow Articles by Dalton, W. S.
The Journal of Immunology, 2002, 168: 2544-2553.
Copyright © 2002 by The American Association of Immunologists

Adhesion-Mediated Intracellular Redistribution of c-Fas-Associated Death Domain-Like IL-1-Converting Enzyme-Like Inhibitory Protein-Long Confers Resistance to CD95-Induced Apoptosis in Hematopoietic Cancer Cell Lines1

Kenneth H. Shain*,{dagger}, Terry H. Landowski*,{ddagger} and William S. Dalton2,*,{dagger},{ddagger}

Departments of * Interdisciplinary Oncology and {dagger} Biochemistry and Molecular Biology, and {ddagger} Clinical Investigation Program, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, FL 33612

Evasion of immune surveillance is a key step in malignant progression. Interactions between transformed hematopoietic cells and their environment may initiate events that confer resistance to apoptosis and facilitate immune evasion. In this report, we demonstrate that {beta}1 integrin-mediated adhesion to fibronectin inhibits CD95-induced caspase-8 activation and apoptosis in hematologic tumor cell lines. This adhesion-dependent inhibition of CD95-mediated apoptosis correlated with enhanced c-Fas-associated death domain-like IL-1-converting enzyme-like inhibitory protein-long (c-FLIPL) cytosolic solubility compared with nonadhered cells. Cytosolic c-FLIPL protein preferentially associated with cytosolic Fas-associated death domain protein (FADD) and localized to the death-inducing signal complex after CD95 ligation in adherent cells. The incorporation of c-FLIPL in the death-inducing signal complex prevented procaspase-8 processing and activation of the effector phase of apoptosis. Adhesion to fibronectin increased c-FLIPL cytosolic solubility and availability for FADD binding by redistributing c-FLIPL from a preexisting membrane-associated fraction. Increased cytosolic availability of c-FLIPL for FADD binding was not related to increased levels of RNA or protein synthesis. These data show that adhesion of anchorage-independent cells to fibronectin provides a novel mechanism of resistance to CD95-mediated programmed cell death by regulating the cellular localization and availability of c-FLIPL.




This article has been cited by other articles:


Home page
 Cancer Res.Home page
K. H. Shain, D. N. Yarde, M. B. Meads, M. Huang, R. Jove, L. A. Hazlehurst, and W. S. Dalton
{beta}1 Integrin Adhesion Enhances IL-6-Mediated STAT3 Signaling in Myeloma Cells: Implications for Microenvironment Influence on Tumor Survival and Proliferation
Cancer Res., February 1, 2009; 69(3): 1009 - 1015.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. B. Meads, L. A. Hazlehurst, and W. S. Dalton
The Bone Marrow Microenvironment as a Tumor Sanctuary and Contributor to Drug Resistance
Clin. Cancer Res., May 1, 2008; 14(9): 2519 - 2526.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
L. E. Perez, N. Parquet, K. Shain, R. Nimmanapalli, M. Alsina, C. Anasetti, and W. Dalton
Bone Marrow Stroma Confers Resistance to Apo2 Ligand/TRAIL in Multiple Myeloma in Part by Regulating c-FLIP
J. Immunol., February 1, 2008; 180(3): 1545 - 1555.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
W. Dalton and K. C. Anderson
Synopsis of a Roundtable on Validating Novel Therapeutics for Multiple Myeloma.
Clin. Cancer Res., November 15, 2006; 12(22): 6603 - 6610.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. A. Hazlehurst, R. F. Argilagos, M. Emmons, D. Boulware, C. A. Beam, D. M. Sullivan, and W. S. Dalton
Cell Adhesion to Fibronectin (CAM-DR) Influences Acquired Mitoxantrone Resistance in U937 Cells
Cancer Res., February 15, 2006; 66(4): 2338 - 2345.
[Abstract] [Full Text] [PDF]

Home page
 ASH ANNUAL MEETING ABSTRACTSHome page
N. Parquet, R. Nimmanapalli, C. Anasetti, M. Alsina, W. Dalton, and L. E. Perez
Bortezomib Partially Overcomes TNF-Related Apoptosis Inducing ligand/Apo-2L (TRAIL/Apo-2L) Environment Mediated-Drug Resistance (EM-DR).
Blood (ASH Annual Meeting Abstracts), November 16, 2004; 104(11): 2459 - 2459.
[Abstract] [Full Text]

Home page
 Clin. Cancer Res.Home page
T. Hayashi, T. Hideshima, A. N. Nguyen, O. Munoz, K. Podar, M. Hamasaki, K. Ishitsuka, H. Yasui, P. Richardson, S. Chakravarty, et al.
Transforming Growth Factor {beta} Receptor I Kinase Inhibitor Down-Regulates Cytokine Secretion and Multiple Myeloma Cell Growth in the Bone Marrow Microenvironment
Clin. Cancer Res., November 15, 2004; 10(22): 7540 - 7546.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
S. Shah and P. W. Sylvester
Tocotrienol-Induced Caspase-8 Activation Is Unrelated to Death Receptor Apoptotic Signaling in Neoplastic Mammary Epithelial Cells
Experimental Biology and Medicine, September 1, 2004; 229(8): 745 - 755.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Fornaro, J. Plescia, S. Chheang, G. Tallini, Y.-M. Zhu, M. King, D. C. Altieri, and L. R. Languino
Fibronectin Protects Prostate Cancer Cells from Tumor Necrosis Factor-{alpha}-induced Apoptosis via the AKT/Survivin Pathway
J. Biol. Chem., December 12, 2003; 278(50): 50402 - 50411.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. A. Hazlehurst, S. A. Enkemann, C. A. Beam, R. F. Argilagos, J. Painter, K. H. Shain, S. Saporta, D. Boulware, L. Moscinski, M. Alsina, et al.
Genotypic and Phenotypic Comparisons of de Novo and Acquired Melphalan Resistance in an Isogenic Multiple Myeloma Cell Line Model
Cancer Res., November 15, 2003; 63(22): 7900 - 7906.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
R. A. Screaton, S. Kiessling, O. J. Sansom, C. B. Millar, K. Maddison, A. Bird, A. R. Clarke, and S. M. Frisch
Fas-associated death domain protein interacts with methyl-CpG binding domain protein 4: A potential link between genome surveillance and apoptosis
PNAS, April 29, 2003; 100(9): 5211 - 5216.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
N. Mitsiades, C. S. Mitsiades, P. G. Richardson, V. Poulaki, Y.-T. Tai, D. Chauhan, G. Fanourakis, X. Gu, C. Bailey, M. Joseph, et al.
The proteasome inhibitor PS-341 potentiates sensitivity of multiple myeloma cells to conventional chemotherapeutic agents: therapeutic applications
Blood, March 15, 2003; 101(6): 2377 - 2380.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
K. C. Anderson and W. S. Dalton
Synopsis of a Research Roundtable Presented on Cell Signaling in Myeloma: Regulation of Growth and Apoptosis--Opportunities for New Drug Discovery
Mol. Cancer Ther., December 1, 2002; 1(14): 1361 - 1365.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
D. G. Stupack and D. A. Cheresh
Get a ligand, get a life: integrins, signaling and cell survival
J. Cell Sci., January 10, 2002; 115(19): 3729 - 3738.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2002 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2002 by The American Association of Immunologists, Inc. All rights reserved.