Wnt5A promotes an adaptive, senescent‐like stress response, while continuing to drive invasion in melanoma cells

• DOI: 10.1111/pcmr.12330
• Publication Date: 2014-11-19T07:20:02Z
• Authors: Marie R. Webster; Mai Xu; Kathryn A. Kinzler; Amanpreet Kaur; Jessica Appleton; Michael P. O'Connell; Katie Marchbank; Alexander Valiga; Vanessa M. Dang; Michela Perego; Gao Zhang; Ana Slipicevic; Frederick Keeney; Elin Lehrmann; William Wood; Kevin G. Becker; Andrew V. Kossenkov; Dennie T. Frederick; Keith T. Flaherty; Xiaowei Xu; Meenhard Herlyn; Maureen E. Murphy; Ashani T. Weeraratna
• Keywords: Cyclin-Dependent Kinase Inhibitor p21; 0301 basic medicine; Skin Neoplasms; Mice, Nude; Wnt-5a Protein; Clone Cells; Wnt Proteins; 03 medical and health sciences; Phenotype; Stress, Physiological; Proto-Oncogene Proteins; Biomarkers, Tumor; Animals; Humans; Female; Neoplasm Invasiveness; Melanoma; Cellular Senescence; Tumor Stem Cell Assay

We have previously shown that Wnt5A drives invasion in melanoma. also promotes resistance to therapy designed target the BRAF(V600E) mutation Here, we show melanomas characterized by high levels of respond therapeutic stress increasing p21 and expressing classical markers senescence, including positivity for senescence-associated β-galactosidase (SA-β-gal), heterochromatic foci (SAHF), H3K9Me chromatin marks, PML bodies. find despite this, these cells retain their ability migrate invade. Further, expression classic senescence such as SA-β-gal SAHF, Wnt5A-high are able colonize lungs vivo tail vein colony-forming assays. This clearly underscores fact do not indicate true cells, but instead an adaptive response allows evade Notably, silencing reduces decreases invasiveness. The combined data point a master regulator melanoma, which may contribute resistance.