当前位置: X-MOL 学术PNAS › 论文详情
Trop2 is a driver of metastatic prostate cancer with neuroendocrine phenotype via PARP1 [Cell Biology]
PNAS ( IF 9.580 ) Pub Date : 2020-01-13 , DOI: 10.1073/pnas.1905384117
En-Chi Hsu, Meghan A. Rice, Abel Bermudez, Fernando Jose Garcia Marques, Merve Aslan, Shiqin Liu, Ali Ghoochani, Chiyuan Amy Zhang, Yun-Sheng Chen, Aimen Zlitni, Sahil Kumar, Rosalie Nolley, Frezghi Habte, Michelle Shen, Kashyap Koul, Donna M. Peehl, Amina Zoubeidi, Sanjiv S. Gambhir, Christian A. Kunder, Sharon J. Pitteri, James D. Brooks, Tanya Stoyanova

Resistance to androgen deprivation therapy, or castration-resistant prostate cancer (CRPC), is often accompanied by metastasis and is currently the ultimate cause of prostate cancer-associated deaths in men. Recently, secondary hormonal therapies have led to an increase of neuroendocrine prostate cancer (NEPC), a highly aggressive variant of CRPC. Here, we identify that high levels of cell surface receptor Trop2 are predictive of recurrence of localized prostate cancer. Moreover, Trop2 is significantly elevated in CRPC and NEPC, drives prostate cancer growth, and induces neuroendocrine phenotype. Overexpression of Trop2 induces tumor growth and metastasis while loss of Trop2 suppresses these abilities in vivo. Trop2-driven NEPC displays a significant up-regulation of PARP1, and PARP inhibitors significantly delay tumor growth and metastatic colonization and reverse neuroendocrine features in Trop2-driven NEPC. Our findings establish Trop2 as a driver and therapeutic target for metastatic prostate cancer with neuroendocrine phenotype and suggest that high Trop2 levels could identify cancers that are sensitive to Trop2-targeting therapies and PARP1 inhibition.
更新日期:2020-01-14

 

全部期刊列表>>
2020新春特辑
限时免费阅读临床医学内容
ACS材料视界
科学报告最新纳米科学与技术研究
清华大学化学系段昊泓
自然科研论文编辑服务
中国科学院大学楚甲祥
中国科学院微生物研究所潘国辉
中国科学院化学研究所
课题组网站
X-MOL
北京大学分子工程苏南研究院
华东师范大学分子机器及功能材料
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug