Inactivation of Rb in Stromal Fibroblasts Promotes Epithelial Cell Invasion

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2012 May 31

PMID 22643222

Citations 20

Authors

Adam Pickard

Ann-Christin Cichon

Anna Barry

Declan Kieran

Daksha Patel

Peter Hamilton

Manuel Salto-Tellez

Jacqueline James

Dennis J McCance

Affiliations

Soon will be listed here.

Abstract

Stromal-derived growth factors are required for normal epithelial growth but are also implicated in tumour progression. We have observed inactivation of the retinoblastoma protein (Rb), through phosphorylation, in cancer-associated fibroblasts in oro-pharyngeal cancer specimens. Rb is well known for its cell-autonomous effects on cancer initiation and progression; however, cell non-autonomous functions of Rb are not well described. We have identified a cell non-autonomous role of Rb, using three-dimensional cultures, where depletion of Rb in stromal fibroblasts enhances invasive potential of transformed epithelia. In part, this is mediated by upregulation of keratinocyte growth factor (KGF), which is produced by the depleted fibroblasts. KGF drives invasion of epithelial cells through induction of MMP1 expression in an AKT- and Ets2-dependent manner. Our data identify that stromal fibroblasts can alter the invasive behaviour of the epithelium, and we show that altered expression of KGF can mediate these functions.

Citing Articles

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