The Notch Pathway Inhibits TGFβ Signaling in Breast Cancer through HEYL-Mediated Crosstalk
Year: 2014
Type: article
Abstract: Acquired resistance to TGFβ is a key step in the early stages of tumorigenesis. Mutations in TGFβ signaling components are rare, and little is known about the development of resistance in breast cancer. On the other hand, an activated Notch pathway is known to play a substantial role in promoting breast cancer development. Here, we present evidence of crosstalk between these two pathways through HEYL. HEYL, a basic helix-loop-helix transcription factor and a direct target of Notch signaling, is specifically overexpressed in breast cancer. HEYL represses TGFβ activity by binding to TGFβ-activated Smads. HeyL(-/-) mice have defective mammary gland development with fewer terminal end buds. On the other hand, HeyL transgenic mice show accelerated mammary gland epithelial proliferation and 24% of multiparous mice develop mammary gland cancer. Therefore, repression of TGFβ signaling by Notch acting through HEYL may promote initiation of breast cancer.
Source: Cancer Research
Institutions: Johns Hopkins University, Johns Hopkins Medicine, Leidos (United States), Science Applications International Corporation (United States), National Cancer Institute, Manchester Academic Health Science Centre, University of Manchester, University of Würzburg, Comprehensive Cancer Center Mainfranken
Language: English
Topic: TGF-β signaling in diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2066855407