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Review
. 2003;5(3):174-9.
doi: 10.1186/bcr598. Epub 2003 Apr 4.

Inflammatory breast cancer: relationship between growth factor signaling and motility in aggressive cancers

Kenneth L van Golen  1
Affiliations
Review

Inflammatory breast cancer: relationship between growth factor signaling and motility in aggressive cancers

Kenneth L van Golen. Breast Cancer Res. 2003.

Abstract

A variety of phenotypic characteristics are required for a cancer cell to successfully complete the metastatic cascade. Acquisition of a motile and invasive phenotype is one requirement for a cell to become metastatically competent. The Rho (Ras homology) GTPases are a subfamily of small GTP-binding proteins, which are related to the Ras oncogene. All aspects of cellular motility and invasion are controlled by the Rho GTPases and are closely linked to signals from the extracellular environment, particularly in response to growth factors. Dysregulation of Rho activation through aberrant growth-factor signaling, loss of function of key Rho-regulatory proteins or overexpression of Rho mRNA could result in increased Rho activity and cellular motility. Therefore, the importance of the Rho GTPases in the progression of aggressive cancers, is becoming more appreciated.

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Figures

Figure 1
Figure 1
The GTPase cycle. RhoGDIs (1) sequester Rho GTPases in the cytoplasm and prevent GDP dissociation until released by RhoGDFs (2). The Rho protein attaches to the inner cytoplasmic membrane by prenylation of the protein. When a protein tyrosine kinase growth factor receptor (3), such as EGFR, is activated, p120 RasGAP is phosphorylated and forms a heterodimer with p190 RhoGAP, leading to inactivation of those proteins. The RhoGEF proteins (4) are also phosphorylated, causing exchange of GDP for GTP (6) on the Rho proteins, leading to Rho activation. Active, GTP-bound Rho proteins activate downstream Rho effector proteins (7), which stimulate cellular motility and invasion (8). RhoGAP (9) is released and activated, catalyzing the hydrolysis of GTP to GDP (10) and inactivating the Rho protein. EGFR = EGF receptor; GAP = GTPase activating factor; GDF = GDI-dissociation factor; GDI = guanine nucleotide dissociation inhibitor; GDP = guanosine diphosphate ; GEF = guanine nucleotide exchange factor; GTP = guanosine triphosphate.
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