Oncotarget

Research Papers:

The Polycomb group protein RING1B is overexpressed in ductal breast carcinoma and is required to sustain FAK steady state levels in breast cancer epithelial cells

Almudena Bosch, Konstantina Panoutsopoulou, Josep Maria Corominas, Ramón Gimeno, Gema Moreno-Bueno, Juan Martín-Caballero, Saleta Morales, Tania Lobato, Carles Martínez-Romero, Eduardo F. Farias, Xavier Mayol, Amparo Cano and Inmaculada Hernández-Muñoz _

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Oncotarget. 2014; 5:2065-2076. https://doi.org/10.18632/oncotarget.1779

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Abstract

Almudena Bosch1,6, Konstantina Panoutsopoulou1, Josep Maria Corominas4, Ramón Gimeno5, Gema Moreno-Bueno2, Juan Martín-Caballero3, Saleta Morales2, Tania Lobato1, Carles Martínez-Romero1, Eduardo F. Farias6, Xavier Mayol1, Amparo Cano2, Inmaculada Hernández-Muñoz1

1. Cancer Research Program. IMIM (Institut Hospital del Mar d’Investigacions Mèdiques). Barcelona. Spain.

2. Departamento de Bioquímica. Facultad de Medicina. Universidad Autónoma. Instituto de Investigaciones Biomédicas “Alberto Sols”, CSIC-UAM. Instituto de Investigación Sanitaria La Paz. Madrid. Spain

3. Laboratory Animal Units. Parc de Recerca Biomèdica de Barcelona. Spain.

4. Servei de Patologia, Hospital del Mar. Barcelona. Spain

5. Servei de Inmunologia. Hospital del Mar. Barcelona. Spain.

6. Current address: Department of Medicine. Mount Sinai School of Medicine. New York. USA.

Correspondence:

Inmaculada Hernández-Muñoz, email:

Keywords: Ring1B/ductal breast carcinoma/ Fak/p63/mammary epithelial cell

Received: February 6, 2014 Accepted: February 12, 2014 Published: February 14, 2014

Abstract

In early stages of metastasis malignant cells must acquire phenotypic changes to enhance their migratory behavior and their ability to breach the matrix surrounding tumors and blood vessel walls. Epigenetic regulation of gene expression allows the acquisition of these features that, once tumoral cells have escape from the primary tumor, can be reverted. Here we report that the expression of the Polycomb epigenetic repressor Ring1B is enhanced in tumoral cells that invade the stroma in human ductal breast carcinoma and its expression is coincident with that of Fak in these tumors. Ring1B knockdown in breast cancer cell lines revealed that Ring1B is required to sustain Fak expression in basal conditions as well as in Tgfβ-treated cells. Functionally, endogenous Ring1B is required for cell migration and invasion in vitro and for in vivo invasion of the mammary fat pad by tumoral cells. Finally we identify p63 as a target of Ring1B to regulate Fak expression: Ring1B depletion results in enhanced p63 expression, which in turns represses Fak expression. Importantly, Fak downregulation upon Ring1B depletion is dependent on p63 expression. Our findings provide new insights in the biology of the breast carcinoma and open new avenues for breast cancer prognosis and therapy.


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