Apoptosis induced by denied adhesion to extracellular matrix (anoikis) in thyroid epithelial cells is p53 dependent but fails to correlate with modulation of p53 expression

Vitale, Mario; Matola, Tiziana Di; Bifulco, Maurizio; Casamassima, Adele; Fenzi, Gianfranco; Rossi, Guido

doi:10.1016/s0014-5793(99)01512-4

Cited by 23 publications

(22 citation statements)

References 18 publications

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“…This type of apoptosis (anoikis) results from a variety of events (Frisch and Francis, 1994). Cells in suspension reorganize cytoskeletal architecture (Boudreau and Jones, 1999;Flusberg et al, 2001), alter growth factor receptor and death receptor distribution and activity (Aoudjit and Vuori, 2001;Arora et al, 1995;Finbloom and Wahl, 1989;Schleiffenbaum and Fehr, 1990) and membrane lipid composition (Schulze et al, 2001), elevate cyclic AMP levels, uncouple GTPase signaling (Howe and Juliano, 2000;Lin et al, 1997;Schwartz and Shattil, 2000) and alter nuclear transcription (Sadek and Allen-Hoffmann, 1994;Segaert et al, 1998;Vitale et al, 1999). These distinct events provide a formidable array of apoptotic triggers that insure that unanchored cells remain non-viable.…”

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confidence: 99%

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

Stupack

Cheresh

2002

Journal of Cell Science

532

434

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Programmed cell death is crucial for the development and maintenance of multicellular organisms. The decision to live, or to die, depends, at the cellular level, upon the cell's interaction with extracellular cues that trigger cell signaling pathways promoting survival or death. The extracellular matrix (ECM) influences the execution of the apoptotic program through the actions of adhesion receptors. Among these, integrins initiate a variety of downstream signaling events in response to ECM ligation. Integrins directly activate survival pathways via the PI 3-kinase and MAPK pathways and act as essential cofactors for their stimulation by growth factors. Conversely,elevated integrin expression in the absence of appropriate ligands, or in the presence of natural or synthetic antagonists, can promote apoptosis under otherwise permissive growth conditions. Integrins thus act in a crucial biosensory role, coordinating survival or death responses as a function of ECM composition. This dual function provides an elegant mechanism through which tissue-remodeling events may regulate cell death or survival in a temporal,ECM-governed manner.

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mentioning

confidence: 99%

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

Stupack

Cheresh

2002

Journal of Cell Science

532

434

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“…One study suggested that p53 increased the survival of transformed fibroblasts and immortalized mammary epithelial cells in suspension by increasing the frequency of colony formation in semisolid medium (25). Thyroid epithelial cells undergo apoptosis through a p53-dependent pathway when integrin-mediated adhesion to the ECM is denied (26). Thus, p53 signaling pathways may regulate anoikis in SCC cells.…”

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confidence: 99%

Squamous Cell Carcinoma Cell Aggregates Escape Suspension-induced, p53-mediated Anoikis

Zhang

Lü

Dazin

et al. 2004

Journal of Biological Chemistry

116

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Disrupting cell adhesion to the extracellular matrix (ECM) 1 rapidly induces programmed cell death, a response that has been termed anoikis (1). Anoikis was first documented in normal epithelial cells and endothelial cells where it helps maintain a dynamic balance between cell turnover and survival (1, 2). Malignant tumor cells are often resistant to anoikis, enabling them to survive after detachment from the ECM and colonize a secondary site. Resistance to anoikis has been described in many types of human malignancies, including gastric cancer, mammary tumors, colon cancers, osteosarcomas, and lung carcinomas (3-7), but little is known about it in the progression of human oral squamous cell (SCC) carcinoma. Oral cancer is the sixth most common solid tumor, accounting for 5.5% of all malignancies worldwide (8). SCC accounts for 96% of all tumors of the oral cavity (9), and many patients with these tumors die from metastatic disease (10).What factors promote anchorage-independent survival and spread of tumor cells? One possibility is survival signals mediated through cell-cell contacts. One factor that promotes the survival of ECM-deprived SCC cells by such contact is the cadherin receptor family (11). A second possibility is the integrin receptor family, because integrins play a role in multiple steps in tumorigenesis, including cell spreading, invasion, and survival. Integrins are heterodimeric, cation-dependent cell membrane adhesion molecules that mediate cell-cell and cell-ECM interactions (12). In mammals, at least 16 ␣ and 8 ␤ subunits have been reported that combine into 22 different heterodimers, each with specific recognition and affinities for various ECM components or other cell-bearing adhesion molecules (13,14). Integrin expression patterns are often altered during tumor development. Metastasis requires changes in integrin expression. In SCC cells, substantial evidence demonstrates altered integrin expression in tumorigenesis compared with the native state. Alterations in the expression and function of integrins are also associated with anoikis (15, 16).One likely mechanism for integrin-mediated survival and resistance to anoikis is signal transduction through activation of intracellular tyrosine kinases, such as focal adhesion kinase (FAK). FAK is a non-receptor protein-tyrosine kinase that indirectly localizes to sites of integrin clustering through C-terminal domain-mediated interaction with integrin-associated proteins such as paxillin and talin (17). In vitro, its N-terminal domain binds to sequences in the cytoplasmic domain of ␤ integrin subunits (18). Elevation of the phosphotyrosine content of FAK correlates directly with increased cell adhesion. Focal adhesion complexes formed in mouse fibroblasts plated on fibronectin have 2.5-fold higher FAK phosphorylation activity than cells plated on polylysine, where adherence is integrinindependent and the phosphotyrosine content of FAK is minimal (19). Tyrosine 397 is the major site for phosphorylation and catalytic activity of FAK both in vivo and...

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“…The relevance of our ®ndings made in an established rat cell line to thyroid cells in vivo remains to be established. Although primary (Di Matola et al, 2000) and established (Vitale et al, 1999) human thyroid cells reportedly undergo more extensive anoikis than established rat thyroid cell lines, the e ects of Ras on anoikis have not been reported. However, primary human thyrocytes, like WRT cells, are resistant to a variety of apoptotic insults including activation of death receptors (Arscott et al, 1997;Bretz et al, 1999).…”

Section: Discussionmentioning

confidence: 98%

“…Unlike many cells where serum or growth factor deprivation is su cient to cellular demise, adherent thyroid cells are also resistant to apoptosis (Dremier et al, 1994;Jeso et al, 1995;Li et al, 1999;Vitale et al, 1999;. Fas ligation or addition of TRAIL, robust stimulators of apoptosis in many cells, required the concerted action of cycloheximide to stimulate apoptosis in human thyroid cells (Arscott et al, 1997;Bretz et al, 1999).…”

Section: Discussionmentioning

confidence: 99%