Mutant Lef1 Controls Gata6 in Sebaceous Gland Development and Cancer

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2019 Mar 20

PMID 30886049

Citations 13

Authors

Benedicte Oules

Emanuel Rognoni

Esther Hoste

Georgina Goss

Ryan Fiehler

Ken Natsuga

Sven Quist

Remco Mentink

Giacomo Donati

Fiona M Watt

Affiliations

Soon will be listed here.

Abstract

Mutations in Lef1 occur in human and mouse sebaceous gland (SG) tumors, but their contribution to carcinogenesis remains unclear. Since Gata6 controls lineage identity in SG, we investigated the link between these two transcription factors. Here, we show that Gata6 is a β-catenin-independent transcriptional target of mutant Lef1. During epidermal development, Gata6 is expressed in a subset of Sox9-positive Lef1-negative hair follicle progenitors that give rise to the upper SG Overexpression of Gata6 by lentiviral injection is sufficient to induce ectopic sebaceous gland elements. In mice overexpressing mutant Lef1, Gata6 ablation increases the total number of skin tumors yet decreases the proportion of SG tumors. The increased tumor burden correlates with impaired DNA mismatch repair and decreased expression of Mlh1 and Msh2 genes, defects frequently observed in human sebaceous neoplasia. Gata6 specifically marks human SG tumors and also defines tumors with elements of sebaceous differentiation, including a subset of basal cell carcinomas. Our findings reveal that Gata6 controls sebaceous gland development and cancer.

Citing Articles

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