Control of cell cycle progression by fibronectin matrix architecture.
Developmental patterning and differentiation, maintenance of parenchymal cell function, and the size, shape, and invasiveness of tumors are all orchestrated by cell interactions with the extracellular matrix. Here we show that the fibrillar structure of fibronectin (FN) matrix encodes essential regulatory cues and controls cell proliferation and signaling through changes in matrix architecture. A matrix assembled from native FN stimulated cell growth. In contrast, a mutant FN (FNDeltaIII1-7) that contains all known cell binding motifs but forms a structurally distinct matrix inhibited progression from G0/G1 into S phase. Furthermore, FNDeltaIII1-7 suppressed the stimulatory capacity of native FN and induced different levels of tyrosine phosphorylation of pp125(FAK). The differential effects on cell growth were ablated by blocking formation of matrix fibrils. Thus, modification of matrix architecture provides a novel approach to control cell proliferation.
Sechler
J L
JL
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Schwarzbauer
J E
JE
D001973:Bromodeoxyuridine / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D005109:Extracellular Matrix / Q000502:physiology; D005353:Fibronectins / Q000737:chemistry* / Q000235:genetics; D005455:Fluorescent Antibody Technique; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006651:Histocytochemistry; D007399:Interphase / Q000502:physiology; D009154:Mutation / Q000235:genetics; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins; D050717:Retinoblastoma-Like Protein p130; D016196:S Phase / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D015815:Cell Adhesion Molecules; D005353:Fibronectins; D010750:Phosphoproteins; D011506:Proteins; D050717:Retinoblastoma-Like Protein p130; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D001973:Bromodeoxyuridine