So You Can Teach Old Fibroblasts New Tricks.
New data show that as dermal fibroblasts grow old, they increase their secretion of the WNT antagonist sFRP2 to drive melanoma cell metastasis. sFRP2 suppresses β-catenin and MITF signaling in melanoma cells, downregulating the redox regulator APE1, making melanoma cells more sensitive to oxidative stress and driving resistance to BRAF inhibitors. Thus, the aging microenvironment in elderly patient skin activates a signaling pathway that drives more aggressive melanoma cell behavior. Cancer Discov; 6(6); 581-3. ©2016 AACR.
Molecular Oncology Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, United Kingdom. Amaya.Viros@cruk.manchester.ac.uk.
Amaya
A
Virós
Molecular Oncology Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, United Kingdom.
Maria Romina
MR
Girotti
Molecular Oncology Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, United Kingdom.
Richard
R
Marais
D000818:Animals; D015415:Biomarkers; D016922:Cellular Senescence; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D060449:Wnt Signaling Pathway / Q000187:drug effects; D000094742:Secreted Frizzled-Related Proteins
D015415:Biomarkers; D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins