NSD2 is a conserved driver of metastatic prostate cancer progression

被引：75

作者：

Aytes, Alvaro ^{[1
,2
,3
]}

Giacobbe, Arianna ^{[1
,4
]}

Mitrofanova, Antonina ^{[5
,6
]}

Ruggero, Katia ^{[2
,3
]}

Cyrta, Joanna ^{[7
]}

Arriaga, Juan ^{[1
,4
]}

Palomero, Luis ^{[2
,3
]}

Farran-Matas, Sonia ^{[2
,3
]}

Rubin, Mark A. ^{[7
,8
]}

Shen, Michael M. ^{[1
,4
,5
,9
,10
]}

Califano, Andrea ^{[5
,10
,11
]}

Abate-Shen, Cory ^{[1
,4
,5
,10
,12
]}

机构：

[1] Columbia Univ, Dept Urol, Irving Med Ctr, 160 Ft Washington Ave, New York, NY 10032 USA

[2] Bellvitge Inst Biomed Res, Catalan Inst Oncol, Program Mol Mech & Expt Therapeut Oncol ONCOBell, Barcelona 08908, Spain

[3] Bellvitge Inst Biomed Res, Catalan Inst Oncol, Program Canc Therapeut Resistance ProCURE, Barcelona 08908, Spain

[4] Columbia Univ, Irving Med Ctr, Dept Med, 630W 168th St, New York, NY 10032 USA

[5] Columbia Univ, Irving Med Ctr, Dept Syst Biol, 1130 St Nicholas Ave, New York, NY 10032 USA

[6] Rutgers State Univ, Dept Hlth Informat, Rutgers Sch Hlth Profess, 65 Bergen St, Newark, NJ 07101 USA

[7] Weill Cornell Med, Dept Pathol & Lab Med, 1300 York Ave, New York, NY 10065 USA

[8] Univ Bern, Dept BioMed Res, Murtenstr 35, CH-3008 Bern, Switzerland

[9] Columbia Univ, Dept Genet & Dev, Irving Med Ctr, 701 West 168th St, New York, NY 10032 USA

[10] Columbia Univ, Herbert Irving Comprehens Canc Ctr, Irving Med Ctr, 1130 St Nicholas Ave, New York, NY 10032 USA

[11] Columbia Univ, Dept Biochem & Mol Biophys, Irving Med Ctr, 701 West 168th St, New York, NY 10032 USA

[12] Columbia Univ, Dept Pathol & Cell Biol, Irving Med Ctr, 630W 168th St, New York, NY 10032 USA

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

关键词：

HISTONE METHYLTRANSFERASE; MOUSE MODEL; EXPRESSION; RESISTANCE; BIOLOGY; CLASSIFICATION; MUTATIONS; THERAPIES; MECHANISM; EVOLUTION;

D O I：

10.1038/s41467-018-07511-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Deciphering cell-intrinsic mechanisms of metastasis progression in vivo is essential to identify novel therapeutic approaches. Here we elucidate cell-intrinsic drivers of metastatic prostate cancer progression through analyses of genetically engineered mouse models (GEMM) and correlative studies of human prostate cancer. Expression profiling of lineage-marked cells from mouse primary tumors and metastases defines a signature of de novo metastatic progression. Cross-species master regulator analyses comparing this mouse signature with a comparable human signature identifies conserved drivers of metastatic progression with demonstrable clinical and functional relevance. In particular, nuclear receptor binding SET Domain Protein 2 (NSD2) is robustly expressed in lethal prostate cancer in humans, while its silencing inhibits metastasis of mouse allografts in vivo. We propose that cross-species analysis can elucidate mechanisms of metastasis progression, thus providing potential additional therapeutic opportunities for treatment of lethal prostate cancer.

引用

页数：14

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