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Anti-apoptotic signaling of the IGF-I receptor in fibroblasts following loss of matrix adhesion

Oncogene volume 18, pages 1827–1836 (1999)Cite this article

Abstract

The type 1 insulin-like growth factor receptor (IGF-IR) is known to protect cells from a variety of apoptotic injuries. In several instances, the anti-apoptotic effect of the wild type IGF-IR is more evident under conditions of anchorage-independence than in cells in monolayer cultures. We have investigated IGF-IR signaling in cells in anoikis, a form of apoptosis that occurs when cells are denied attachment to the extra-cellular matrix. IGF-I protects mouse embryo fibroblasts (MEF) from anoikis caused by withdrawal of growth factors. Survival is dependent on the concentration of IGF-I and a sufficient number of functional IGF-I receptors. In this model, IGF-I protection correlates best with ras activation and cell-to-cell aggregation, while PI3-kinase, Akt and MAP kinases seem to play a lesser, alternative role.

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Abbreviations

ECM:

extracellular matrix

FAK:

focal adhesion kinase

IGF I:

insulin-like growth factor I

IGF IR:

type 1 insulin-like growth factor receptor

IRS-1:

insulin receptor substrate 1

MEF:

mouse embryo fibroblasts

PI:

phophatidylinositol

PolyHEMA:

polyhydroxyethylmethacrylate

SFM:

serum free medium

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Acknowledgements

This work was supported by grants CA 53484 and GM 33694 from the National Institutes of Health

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Authors and Affiliations

  1. Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, 19107, Pennsylvania, USA

    Barbara Valentinis, Andrea Morrione, Francesca Peruzzi, Marco Prisco, Krzysztof Reiss & Renato Baserga

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  1. Barbara Valentinis
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  2. Andrea Morrione
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Valentinis, B., Morrione, A., Peruzzi, F. et al. Anti-apoptotic signaling of the IGF-I receptor in fibroblasts following loss of matrix adhesion. Oncogene 18, 1827–1836 (1999). https://doi.org/10.1038/sj.onc.1202471

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