Control of Cell Cycle Progression by Fibronectin Matrix Architecture

doi:10.1074/jbc.273.40.25533

Control of Cell Cycle Progression by Fibronectin Matrix Architecture*

From the Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544

Abstract

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 (FNΔIII_1–7) that contains all known cell binding motifs but forms a structurally distinct matrix inhibited progression from G₀/G₁ into S phase. Furthermore, FNΔIII_1–7 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.

Footnotes

↵* This work was supported in part by National Institutes of Health Grant CA 44627 (to J. E. S.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵‡ Fellow of the New Jersey Commission on Cancer Research.
↵§ To whom correspondence should be addressed. Tel.: 609-258-2893; Fax: 609-258-1035; E-mail: jschwarzbauer{at}molbio.princeton.edu.
↵2 J. L. Sechler and J. E. Schwarzbauer, unpublished observations.
Abbreviations:

FN

fibronectin

pFN

plasma FN

FNΔIII_1–7

recombinant FN lacking repeats III_1–7

SVT2

SV40-transformed 3T3 cells

FACS

fluorescence-activated cell sorting

BrdUrd

bromodeoxyuridine

ELISA

enzyme-linked immunosorbent assay

PAGE

polyacrylamide gel electrophoresis.
- Received July 9, 1998.
- Revision received July 29, 1998.
The American Society for Biochemistry and Molecular Biology, Inc.