TRIM28 promotes luminal cell plasticity in a mouse model of prostate cancer.
TRIM28 promotes luminal cell plasticity in a mouse model of prostate cancer.
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DOI：
10.1038/s41388-023-02655-0
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发表时间：
2023-04
期刊：
影响因子：
8
通讯作者：
Shibata, Maho
中科院分区：
文献类型：
--
作者：
Yende, Ashutosh S.;Williams, Emily C.;Pletcher, Andrew;Helfand, Alexandra;Ibeawuchi, Helen;North, Tanya M.;Latham, Patricia S.;Horvath, Anelia;Shibata, Maho
含有三联基序的 28 (TRIM28) 转录辅助因子在高级别和转移性前列腺癌中显着上调。为了研究 TRIM28 在体内前列腺癌进展中的作用，我们建立了一个基因工程小鼠模型，结合了 Trp53、Pten 和 Trim28 的前列腺特异性失活。 Trim28 灭活的 NPp53T 小鼠在前列腺腔中出现炎症反应和坏死。通过进行单细胞RNA测序，我们发现NPp53T前列腺具有较少的类似于近端管腔谱系细胞的管腔细胞，近端管腔谱系细胞是具有祖活性的细胞，在野生型小鼠的近端前列腺和前列腺内陷尖端中富集，与人类前列腺中的类似群体相似。然而，尽管细胞凋亡增加和表达近端管腔细胞标记物的细胞减少，我们发现 NPp53T 小鼠前列腺进化并进展为侵袭性前列腺癌，总体生存期缩短。总而言之，我们的研究结果表明 TRIM28 促进前列腺肿瘤细胞中近端管腔细胞标志物的表达，并为 TRIM28 在前列腺肿瘤可塑性中的功能提供了见解。
The Tripartite motif-containing 28 (TRIM28) transcriptional cofactor is significantly upregulated in high-grade and metastatic prostate cancers. To study the role of TRIM28 in prostate cancer progression in vivo, we generated a genetically engineered mouse model, combining prostate-specific inactivation of Trp53, Pten and Trim28. Trim28 inactivated NPp53T mice developed an inflammatory response and necrosis in prostate lumens. By conducting single-cell RNA sequencing, we found that NPp53T prostates had fewer luminal cells resembling proximal luminal lineage cells, which are cells with progenitor activity enriched in proximal prostates and prostate invagination tips in wild-type mice with analogous populations in human prostates. However, despite increased apoptosis and reduction of cells expressing proximal luminal cell markers, we found that NPp53T mouse prostates evolved and progressed to invasive prostate carcinoma with a shortened overall survival. Altogether, our findings suggest that TRIM28 promotes expression of proximal luminal cell markers in prostate tumor cells and provides insights into TRIM28 function in prostate tumor plasticity.
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影响因子：
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作者：
Czerwińska P;Shah PK;Tomczak K;Klimczak M;Mazurek S;Sozańska B;Biecek P;Korski K;Filas V;Mackiewicz A;Andersen JN;Wiznerowicz M
通讯作者：
Wiznerowicz M
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
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Schultz N
单细胞转录组学鉴定远端前列腺内陷尖端中独特的管腔祖细胞类型
影响因子：
30.8
作者：
Guo W;Li L;He J;Liu Z;Han M;Li F;Xia X;Zhang X;Zhu Y;Wei Y;Li Y;Aji R;Dai H;Wei H;Li C;Chen Y;Chen L;Gao D
通讯作者：
Gao D
影响因子：
16
作者：
Bacon, Curtis W.;Challa, Ashwini;D'Orso, Ivan
通讯作者：
D'Orso, Ivan
影响因子：
46.9
作者：
Doench JG;Fusi N;Sullender M;Hegde M;Vaimberg EW;Donovan KF;Smith I;Tothova Z;Wilen C;Orchard R;Virgin HW;Listgarten J;Root DE
通讯作者：
Root DE