Marie R Webster, Mitchell E Fane, Gretchen M Alicea, Subhasree Basu, Andrew V Kossenkov, Gloria E Marino, Stephen M Douglass, Amanpreet Kaur, Brett L Ecker, Keerthana Gnanapradeepan, Abibatou Ndoye, Curtis Kugel, Alexander Valiga, Jessica Palmer, Qin Liu, Xiaowei Xu, Jessicamarie Morris, Xiangfan Yin, Hong Wu, Wei Xu, Cathy Zheng, Giorgos C Karakousis, Ravi K Amaravadi, Tara C Mitchell, Filipe V Almeida, Min Xiao, Vito W Rebecca, Ying-Jie Wang, Lynn M Schuchter, Meenhard Herlyn, Maureen E Murphy, Ashani T Weeraratna
Metastatic melanoma is an aggressive disease, despite recent improvements in therapy. Eradicating all melanoma cells even in drug-sensitive tumors is unsuccessful in patients because a subset of cells can transition to a slow-cycling state, rendering them resistant to most targeted therapy. It is still unclear what pathways define these subpopulations and promote this resistant phenotype. In the current study, we show that Wnt5A, a non-canonical Wnt ligand that drives a metastatic, therapy-resistant phenotype, stabilizes the half-life of p53 and uses p53 to initiate a slow-cycling state following stress (DNA damage, targeted therapy, and aging)...
February 6, 2020: Molecular Cell