The ZNF750-RAC1 axis as potential prognostic factor for breast cancer.
The ZNF750-RAC1 axis as potential prognostic factor for breast cancer.
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ZnF750-RAC1轴是乳腺癌的潜在预后因素。
DOI：
10.1038/s41420-020-00371-2
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发表时间：
2020-11-29
影响因子：
7
通讯作者：
Melino G
中科院分区：
文献类型：
--
作者：
Butera A;Cassandri M;Rugolo F;Agostini M;Melino G
人锌指（C2H2-type）蛋白ZNF750是一种受p63调控的转录因子，在上皮组织稳态中起关键作用，并参与癌症的发病机制。事实上，在食管鳞状细胞癌中发现了错义突变、截断和基因组缺失。与此同时，我们发现ZNF750负向调节乳腺癌细胞的迁移和侵袭；特别是，ZNF750结合并招募LAMB3和CTNNAL1启动子上的KDM1A和HDAC1。这种相互作用反过来又抑制了参与细胞迁移和侵袭的LAMB3和CTNNAL1基因的转录。鉴于ZNF750作为肿瘤抑制基因的关键转录因子正在出现，本研究表明，ZNF750通过直接结合其启动子区域，抑制乳腺癌细胞系中小GTPase ras相关C3肉毒毒素底物1 （RAC1）的表达。为了与ZNF750控制RAC1表达保持一致，我们发现ZNF750和RAC1在人类乳腺癌数据集中呈负相关。更重要的是，我们在人类乳腺癌数据集中发现了RAC1的显著上调，我们发现了RAC1表达与乳腺癌患者生存率之间的直接相关性。总之，我们的发现提供了ZNF750作为肿瘤抑制基因的一种新的分子机制。因此，我们报告了ZNF750/RAC1轴在乳腺癌中的潜在临床相关性。
The human zinc finger (C2H2-type) protein ZNF750 is a transcription factor regulated by p63 that plays a critical role in epithelial tissues homoeostasis, as well as being involved in the pathogenesis of cancer. Indeed, missense mutations, truncation and genomic deletion have been found in oesophageal squamous cell carcinoma. In keeping, we showed that ZNF750 negatively regulates cell migration and invasion in breast cancer cells; in particular, ZNF750 binds and recruits KDM1A and HDAC1 on the LAMB3 and CTNNAL1 promoters. This interaction, in turn, represses the transcription of LAMB3 and CTNNAL1 genes, which are involved in cell migration and invasion. Given that ZNF750 is emerging as a crucial transcription factor that acts as tumour suppressor gene, here, we show that ZNF750 represses the expression of the small GTPase, Ras-related C3 botulinum toxin substrate 1 (RAC1) in breast cancer cell lines, by directly binding its promoter region. In keeping with ZNF750 controlling RAC1 expression, we found an inverse correlation between ZNF750 and RAC1 in human breast cancer datasets. More importantly, we found a significant upregulation of RAC1 in human breast cancer datasets and we identified a direct correlation between RAC1 expression and the survival rate of breast cancer patient. Overall, our findings provide a novel molecular mechanism by which ZNF750 acts as tumour suppressor gene. Hence, we report a potential clinical relevance of ZNF750/RAC1 axis in breast cancer.
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DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
影响因子：
5.5
作者：
Polewko-Klim A;Lesiński W;Mnich K;Piliszek R;Rudnicki WR
通讯作者：
Rudnicki WR
影响因子：
8
作者：
Cassandri, Matteo;Butera, Alessio;Melino, Gerry
通讯作者：
Melino, Gerry
ZnF750与KLF4和RCOR1，KDM1A和CTBP1/2染色质调节剂相互作用，以抑制表皮祖细胞基因并诱导分化基因。
影响因子：
10.5
作者：
Boxer LD;Barajas B;Tao S;Zhang J;Khavari PA
通讯作者：
Khavari PA
影响因子：
64.5
作者：
Ciriello G;Gatza ML;Beck AH;Wilkerson MD;Rhie SK;Pastore A;Zhang H;McLellan M;Yau C;Kandoth C;Bowlby R;Shen H;Hayat S;Fieldhouse R;Lester SC;Tse GM;Factor RE;Collins LC;Allison KH;Chen YY;Jensen K;Johnson NB;Oesterreich S;Mills GB;Cherniack AD;Robertson G;Benz C;Sander C;Laird PW;Hoadley KA;King TA;TCGA Research Network;Perou CM
通讯作者：
Perou CM