Insulin-like growth factor-I-mediated survival from anoikis: role of cell aggregation and focal adhesion kinase. 1998

B Valentinis, and K Reiss, and R Baserga
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

Anoikis is a form of cell death that occurs when cells are denied attachment to the extra-cellular matrix. Using p6 cells, that are 3T3 cells overexpressing the type 1 insulin-like growth factor receptor (IGF-IR), we show that these cells undergo apoptosis when seeded on polyHEMA plates in serum-free medium (SFM). IGF-I protects p6 cells from anoikis, without inducing mitogenesis or DNA synthesis. In the surviving p6 cells in suspension cultures, the focal adhesion kinase (FAK) is tyrosyl phosphorylated by IGF-I, although this phosphorylation occurs only after several hours. The importance of FAK in protection from anoikis is confirmed by v-src-transformed R-cells, in which FAK is constitutively phosphorylated, that survive even in SFM. Surviving cells, whether p6 or v-src transformed, tend to form large cell aggregates, whose appearance precedes the phosphorylation of FAK. These and other findings suggest that FAK phosphorylation in the case of IGF-I is a mediated effect rather than a direct one. When p6 cells are plated on polyHEMA dishes, IGF-I induces cell aggregation and this aggregation correlates with survival and the eventual phosphorylation of FAK.

UI MeSH Term Description Entries
D007334 Insulin-Like Growth Factor I A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor. IGF-I,Somatomedin C,IGF-1,IGF-I-SmC,Insulin Like Growth Factor I,Insulin-Like Somatomedin Peptide I,Insulin Like Somatomedin Peptide I
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D011102 Polyhydroxyethyl Methacrylate A biocompatible, hydrophilic, inert gel that is permeable to tissue fluids. It is used as an embedding medium for microscopy, as a coating for implants and prostheses, for contact lenses, as microspheres in adsorption research, etc. Glycol Methacrylate Gel,Hydroxymethacrylate Gel,PHEMA,Poly-Hema,Polyglycol Methacrylate,Gel, Glycol Methacrylate,Gel, Hydroxymethacrylate,Methacrylate Gel, Glycol,Methacrylate, Polyglycol,Methacrylate, Polyhydroxyethyl,Poly Hema
D011505 Protein-Tyrosine Kinases Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors. Tyrosine Protein Kinase,Tyrosine-Specific Protein Kinase,Protein-Tyrosine Kinase,Tyrosine Kinase,Tyrosine Protein Kinases,Tyrosine-Specific Protein Kinases,Tyrosylprotein Kinase,Kinase, Protein-Tyrosine,Kinase, Tyrosine,Kinase, Tyrosine Protein,Kinase, Tyrosine-Specific Protein,Kinase, Tyrosylprotein,Kinases, Protein-Tyrosine,Kinases, Tyrosine Protein,Kinases, Tyrosine-Specific Protein,Protein Kinase, Tyrosine-Specific,Protein Kinases, Tyrosine,Protein Kinases, Tyrosine-Specific,Protein Tyrosine Kinase,Protein Tyrosine Kinases,Tyrosine Specific Protein Kinase,Tyrosine Specific Protein Kinases
D002449 Cell Aggregation The phenomenon by which dissociated cells intermixed in vitro tend to group themselves with cells of their own type. Aggregation, Cell,Aggregations, Cell,Cell Aggregations
D002461 Cell Line, Transformed Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals. Transformed Cell Line,Cell Lines, Transformed,Transformed Cell Lines
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005434 Flow Cytometry Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. Cytofluorometry, Flow,Cytometry, Flow,Flow Microfluorimetry,Fluorescence-Activated Cell Sorting,Microfluorometry, Flow,Cell Sorting, Fluorescence-Activated,Cell Sortings, Fluorescence-Activated,Cytofluorometries, Flow,Cytometries, Flow,Flow Cytofluorometries,Flow Cytofluorometry,Flow Cytometries,Flow Microfluorometries,Flow Microfluorometry,Fluorescence Activated Cell Sorting,Fluorescence-Activated Cell Sortings,Microfluorimetry, Flow,Microfluorometries, Flow,Sorting, Fluorescence-Activated Cell,Sortings, Fluorescence-Activated Cell

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