The structural and mechanical complexity of cell-growth control

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Abstract

Tight control of cell proliferation is required to ensure normal tissue patterning and prevent cancer formation. The analysis of cultured cells has led to an explosion in our understanding of the molecules that trigger growth and mediate cell-cycle progression. However, the mechanism by which the local growth differentials that drive morphogenesis are established and maintained still remains unknown. Here we review recent work that reveals the importance of cell binding to the extracellular matrix, and associated changes in cell shape and cytoskeletal tension, to the spatial control of cell-cycle progression. These findings change the paradigm of cell-growth control, by placing our understanding of molecular signalling cascades in the context of the structural and mechanical complexity of living tissues.

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Figure 1: How local growth differentials drive normal tissue patterning during epithelial morphogenesis and angiogenesis.
Figure 2: Control of cell shape independently of the total cell–ECM contact area, studied using micropatterned adhesive substrates.
Figure 3: A pseudocolour image showing establishment of local growth differentials in the presence of soluble mitogens in vitro.
Figure 4: Working model for regulation of G1 progression by growth factors, adhesion to ECM and cell distortion.
Figure 5: Model for tension-driven tissue remodelling during normal morphogenesis and its deregulation during tumour formation.

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Acknowledgements

This work was supported by grants from the NIH (CA58833, CA45548 & HL57669, to D.E.I.) and by a fellowship from the Schweizerische Stiftung für Medizinisch-Biologische Stipendien (to S.H.).

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