Targeting of the Tumor Suppressor GRHL3 by a miR-21-Dependent Proto-Oncogenic Network Results in PTEN Loss and Tumorigenesis
- Author(s)
- Darido, C; Georgy, SR; Wilanowski, T; Dworkin, S; Auden, A; Zhao, Q; Rank, G; Srivastava, S; Finlay, MJ; Papenfuss, AT; Pandolfi, PP; Pearson, RB; Jane, SM;
- Details
- Publication Year 2011-11-15,Volume 20,Issue #5,Page 635-648
- Journal Title
- CANCER CELL
- Publication Type
- Journal Article
- Abstract
- Despite its prevalence, the molecular basis of squamous cell carcinoma (SCC) remains poorly understood. Here, we identify the developmental transcription factor Grhl3 as a potent tumor suppressor of SCC in mice, and demonstrate that targeting of Grhl3 by a miR-21-dependent proto-oncogenic network underpins SCC in humans. Deletion of Grhl3 in adult epidermis evokes loss of expression of PTEN, a direct GRHL3 target, resulting in aggressive SCC induced by activation of P131K/AKT/mTOR signaling. Restoration of Pten expression completely abrogates SCC formation. Reduced levels of GRHL3 and PTEN are evident in human skin, and head and neck SCC, associated with increased expression of miR-21, which targets both tumor suppressors. Our data define the GRHL3-PTEN axis as a critical tumor suppressor pathway in SCC.
- Publisher
- CELL PRESS
- Keywords
- SQUAMOUS-CELL CARCINOMA; KAPPA-B-KINASE; NONMELANOMA SKIN-CANCER; IKK-ALPHA; MICE LACKING; GRAINY-HEAD; EXPRESSION SIGNATURE; TRANSCRIPTION FACTOR; NEGATIVE REGULATION; WOUND REPAIR
- Research Division(s)
- Bioinformatics
- Publisher's Version
- https://doi.org/10.1016/j.ccr.2011.10.014
- Terms of Use/Rights Notice
- Copyright © 2011 Elsevier Inc. All rights reserved.
Creation Date: 2011-11-15 12:00:00