De novo induction of lineage plasticity from human prostate luminal epithelial cells by activated AKT1 and c-Myc.
De novo induction of lineage plasticity from human prostate luminal epithelial cells by activated AKT1 and c-Myc.
复制标题
DOI：
10.1038/s41388-020-01487-6
复制
发表时间：
2020-11
期刊：
影响因子：
8
通讯作者：
Xin L
中科院分区：
文献类型：
--
作者：
Kwon OJ;Zhang L;Jia D;Zhou Z;Li Z;Haffner M;Lee JK;True L;Morrissey C;Xin L
Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that either develops de novo or arises from prostate adenocarcinoma as a result of treatment resistance. Although the prostate basal cells have been shown to directly generate tumor cells with neuroendocrine features when transduced with oncogenic signaling, the identity of the cell-of-origin for de novo NEPC remains unclear. We show that the TACSTD2high human prostate luminal epithelia cells highly express SOX2 and are relatively enriched in the transition zone prostate. Both TACSTD2high and TACSTD2low luminal cells transduced by activated AKT and c-Myc can form organoids containing versatile clinically relevant tumor cell lineages with regard to the expression of AR and the neuroendocrine cell markers Synaptophysin and Chromogranin A. Tumor organoid cells derived from the TACSTD2high luminal cells are more predisposed to neuroendocrine differentiation along passaging and are relatively more castration-resistant. Knocking down TACSTD2 and SOX2 both attenuate neuroendocrine differentiation of tumor organoid cells. This study demonstrates de novo neuroendocrine differentiation of the human prostate luminal epithelial cells induced by caAKT and c-Myc and reveals an impact of cellular status on initiation of lineage plasticity.
登录
查看更多内容
DOI：
10.1126/science.1189992
发表时间：
2010-07-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Goldstein AS;Huang J;Guo C;Garraway IP;Witte ON
通讯作者：
Witte ON
影响因子：
82.9
作者：
Beltran H;Prandi D;Mosquera JM;Benelli M;Puca L;Cyrta J;Marotz C;Giannopoulou E;Chakravarthi BV;Varambally S;Tomlins SA;Nanus DM;Tagawa ST;Van Allen EM;Elemento O;Sboner A;Garraway LA;Rubin MA;Demichelis F
通讯作者：
Demichelis F
影响因子：
64.5
作者：
Karthaus WR;Iaquinta PJ;Drost J;Gracanin A;van Boxtel R;Wongvipat J;Dowling CM;Gao D;Begthel H;Sachs N;Vries RGJ;Cuppen E;Chen Y;Sawyers CL;Clevers HC
通讯作者：
Clevers HC
影响因子：
--
作者：
Liu, June;Pascal, Laura E.;Wang, Zhou
通讯作者：
Wang, Zhou
影响因子：
64.8
作者：
Leong, Kevin G.;Wang, Bu-Er;Gao, Wei-Qiang
通讯作者：
Gao, Wei-Qiang