PSIP1/p75 promotes tumorigenicity in breast cancer cells by promoting the transcription of cell cycle genes.
PSIP1/p75 promotes tumorigenicity in breast cancer cells by promoting the transcription of cell cycle genes.
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PSIP1/p75 通过促进细胞周期基因的转录来促进乳腺癌细胞的致瘤性。
DOI：
10.1093/carcin/bgx062
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发表时间：
2017
期刊：
影响因子：
4.7
通讯作者：
Balla,AndreK
中科院分区：
文献类型：
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作者：
Singh,DeepakK;Gholamalamdari,Omid;Jadaliha,Mahdieh;LingLi,Xiao;Lin,Yo-Chuen;Zhang,Yang;Guang,Shuomeng;Hashemikhabir,Seyedsasan;Tiwari,Saumya;Zhu,YuelinJ;Khan,Abid;Thomas,Anu;Chakraborty,Arindam;Macias,Virgilia;Balla,AndreK
乳腺癌（BC）是一种高度异质性的疾病，无论是在病理和 在分子水平上，几种染色质相关蛋白在BC中起着至关重要的作用 启动和进展。在这里，我们展示了PSIP 1（PC 4和SF 2）的作用， 相互作用蛋白）/p75（LEDGF）在BC进展中的作用。PSIP 1/p75，以前被鉴定为一种 染色质衔接蛋白，被发现在基底样/三阴性乳腺癌中上调， 癌症（TNBC）患者样品和细胞系。组织芯片的免疫组化显示 转移性浸润性导管癌中PSIP 1水平升高。生存数据分析 PSIP 1水平与TNBC患者呈负相关， 生存PSIP 1/p75的缺失显著降低了肿瘤的发生和转移。 TNBC细胞系的特性，而其过表达促进致瘤性。此外，本发明还 基因表达研究表明，PSIP 1调节基因的表达， 细胞周期进程、细胞迁移和侵袭。最后，通过与RNA相互作用， 聚合酶II，PSIP 1/p75促进RNA聚合酶II与细胞启动子的结合， 循环基因，从而调节它们的转录。我们的研究结果表明， PSIP 1/p75通过促进基因表达在TNBC致瘤性中的重要作用 控制着细胞周期和肿瘤转移。
Breast cancer (BC) is a highly heterogeneous disease, both at the pathological and molecular level, and several chromatin-associated proteins play crucial roles in BC initiation and progression. Here, we demonstrate the role of PSIP1 (PC4 and SF2 interacting protein)/p75 (LEDGF) in BC progression. PSIP1/p75, previously identified as a chromatin-adaptor protein, is found to be upregulated in basal-like/triple negative breast cancer (TNBC) patient samples and cell lines. Immunohistochemistry in tissue arrays showed elevated levels of PSIP1 in metastatic invasive ductal carcinoma. Survival data analyses revealed that the levels of PSIP1 showed a negative association with TNBC patient survival. Depletion of PSIP1/p75 significantly reduced the tumorigenicity and metastatic properties of TNBC cell lines while its over-expression promoted tumorigenicity. Further, gene expression studies revealed that PSIP1 regulates the expression of genes controlling cell-cycle progression, cell migration and invasion. Finally, by interacting with RNA polymerase II, PSIP1/p75 facilitates the association of RNA pol II to the promoter of cell cycle genes and thereby regulates their transcription. Our findings demonstrate an important role of PSIP1/p75 in TNBC tumorigenicity by promoting the expression of genes that control the cell cycle and tumor metastasis.