Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance
2017; American Association for the Advancement of Science; Volume: 355; Issue: 6320 Linguagem: Inglês
10.1126/science.aah4199
ISSN1095-9203
AutoresSheng‐Yu Ku, Spencer R. Rosario, Yanqing Wang, Ping Mu, Mukund Seshadri, Zachary W. Goodrich, Maxwell M. Goodrich, David P. Labbé, Eduardo Cortes Gomez, Jianmin Wang, Henry W. Long, Bo Xu, Myles Brown, Massimo Loda, Charles L. Sawyers, Leigh Ellis, David W. Goodrich,
Tópico(s)FOXO transcription factor regulation
ResumoEvading cancer drugs by identity fraud Prostate cancer growth is fueled by male hormones called androgens. Drugs targeting the androgen receptor (AR) are initially efficacious, but most tumors eventually become resistant (see the Perspective by Kelly and Balk). Mu et al. found that prostate cancer cells escaped the effects of androgen deprivation therapy through a change in lineage identity. Functional loss of the tumor suppressors TP53 and RB1 promoted a shift from AR-dependent luminal epithelial cells to AR-independent basal-like cells. In related work, Ku et al. found that prostate cancer metastasis, lineage switching, and drug resistance were driven by the combined loss of the same tumor suppressors and were accompanied by increased expression of the epigenetic regulator Ezh2. Ezh2 inhibitors reversed the lineage switch and restored sensitivity to androgen deprivation therapy in experimental models. Science , this issue p. 84 , p. 78 ; see also p. 29
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