Links between transforming growth factor-beta and canonical Wnt signaling yield new insights into breast cancer susceptibility, suppression and tumor heterogeneity.
In a recent issue of Breast Cancer Research, investigators from the Serra laboratory describe a novel mechanism of transforming growth factor (TGF)-beta tumor suppression. Previously, the authors discovered that stromal TGF-beta signaled through Wnt5a to restrain pubertal ductal elongation and branching. Here, they show that inhibition of stromal TGF-beta signaling or Wnt5a loss leads to increased beta-catenin transcriptional activity and reduced latency in mammary tumor models, with tumors displaying a higher proportion of progenitor cell markers. These findings reveal a novel intersection of two tumor suppressors with a potent oncogenic pathway and highlight the need for further study on the role played by canonical Wnt signaling in breast cancer susceptibility and subtype.
Incassati
Angela
A
Department of Cell Biology, New York University School of Medicine, NY, USA. incasa01@nyumc.org
Pinderhughes
Alicia
A
Eelkema
Rachel
R
Cowin
Pamela
P
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D008495:Medical Oncology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D000071818:Wnt-5a Protein
D011518:Proto-Oncogene Proteins; D016212:Transforming Growth Factor beta; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein