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Trop2 identifies a subpopulation of murine and human prostate basal cells with stem cell characteristics.Trop2可识别具有干细胞特征的小鼠和人类前列腺基底细胞亚群。
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1
Breast Cancer Stem Cell Isolation.乳腺癌干细胞的分离
Methods Mol Biol. 2016;1406:121-35. doi: 10.1007/978-1-4939-3444-7_10.
2
A basal stem cell signature identifies aggressive prostate cancer phenotypes.一种基底干细胞特征可识别侵袭性前列腺癌表型。
Proc Natl Acad Sci U S A. 2015 Nov 24;112(47):E6544-52. doi: 10.1073/pnas.1518007112. Epub 2015 Oct 12.
3
Trop-2 is up-regulated in invasive prostate cancer and displaces FAK from focal contacts.Trop-2在侵袭性前列腺癌中上调，并使黏着斑激酶从黏着斑中移位。
Oncotarget. 2015 Jun 10;6(16):14318-28. doi: 10.18632/oncotarget.3960.
4
Trop2 and its overexpression in cancers: regulation and clinical/therapeutic implications.Trop2 及其在癌症中的过表达：调控与临床/治疗意义
Genes Cancer. 2015 Mar;6(3-4):84-105. doi: 10.18632/genesandcancer.40.
5
Identification of a cyclin D1 network in prostate cancer that antagonizes epithelial-mesenchymal restraint.鉴定前列腺癌中细胞周期蛋白 D1 网络，该网络拮抗上皮-间充质抑制。
Cancer Res. 2014 Jan 15;74(2):508-19. doi: 10.1158/0008-5472.CAN-13-1313. Epub 2013 Nov 26.
6
Metastatic castration-resistant prostate cancer reveals intrapatient similarity and interpatient heterogeneity of therapeutic kinase targets.转移性去势抵抗性前列腺癌揭示了治疗激酶靶点的患者内相似性和患者间异质性。
Proc Natl Acad Sci U S A. 2013 Dec 3;110(49):E4762-9. doi: 10.1073/pnas.1319948110. Epub 2013 Nov 18.
7
Does the microenvironment influence the cell types of origin for prostate cancer?微环境是否影响前列腺癌的细胞起源类型？
Genes Dev. 2013 Jul 15;27(14):1539-44. doi: 10.1101/gad.222380.113.
8
Cyclin D1 determines estrogen signaling in the mammary gland in vivo.细胞周期蛋白D1在体内决定乳腺中的雌激素信号传导。
Mol Endocrinol. 2013 Sep;27(9):1415-28. doi: 10.1210/me.2013-1065. Epub 2013 Jul 17.
9
Novel oncogene-induced metastatic prostate cancer cell lines define human prostate cancer progression signatures.新型癌基因诱导转移性前列腺癌细胞系定义了人类前列腺癌进展特征。
Cancer Res. 2013 Jan 15;73(2):978-89. doi: 10.1158/0008-5472.CAN-12-2133. Epub 2012 Nov 30.
10
Prominin-1 (CD133) Expression in the Prostate and Prostate Cancer: A Marker for Quiescent Stem Cells.Prominin-1（CD133）在前列腺和前列腺癌中的表达：静止干细胞的标志物。
Adv Exp Med Biol. 2013;777:167-84. doi: 10.1007/978-1-4614-5894-4_11.

v-Src癌基因通过细胞周期蛋白D1诱导Trop2蛋白水解激活。

v-Src Oncogene Induces Trop2 Proteolytic Activation via Cyclin D1.

作者信息

Ju Xiaoming, Jiao Xuanmao, Ertel Adam, Casimiro Mathew C, Di Sante Gabriele, Deng Shengqiong, Li Zhiping, Di Rocco Agnese, Zhan Tingting, Hawkins Adam, Stoyanova Tanya, Andò Sebastiano, Fatatis Alessandro, Lisanti Michael P, Gomella Leonard G, Languino Lucia R, Pestell Richard G

机构信息

Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania.

Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.

出版信息

Cancer Res. 2016 Nov 15;76(22):6723-6734. doi: 10.1158/0008-5472.CAN-15-3327. Epub 2016 Sep 15.

DOI:10.1158/0008-5472.CAN-15-3327
PMID:27634768
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5330252/
Abstract

Proteomic analysis of castration-resistant prostate cancer demonstrated the enrichment of Src tyrosine kinase activity in approximately 90% of patients. Src is known to induce cyclin D1, and a cyclin D1-regulated gene expression module predicts poor outcome in human prostate cancer. The tumor-associated calcium signal transducer 2 (TACSTD2/Trop2/M1S1) is enriched in the prostate, promoting prostate stem cell self-renewal upon proteolytic activation via a γ-secretase cleavage complex (PS1, PS2) and TACE (ADAM17), which releases the Trop2 intracellular domain (Trop2 ICD). Herein, v-Src transformation of primary murine prostate epithelial cells increased the proportion of prostate cancer stem cells as characterized by gene expression, epitope characteristics, and prostatosphere formation. Cyclin D1 was induced by v-Src, and Src kinase induction of Trop2 ICD nuclear accumulation required cyclin D1. Cyclin D1 induced abundance of the Trop2 proteolytic cleavage activation components (PS2, TACE) and restrained expression of the inhibitory component of the Trop2 proteolytic complex (Numb). Patients with prostate cancer with increased nuclear Trop2 ICD and cyclin D1, and reduced Numb, had reduced recurrence-free survival probability (HR = 4.35). Cyclin D1, therefore, serves as a transducer of v-Src-mediated induction of Trop2 ICD by enhancing abundance of the Trop2 proteolytic activation complex. Cancer Res; 76(22); 6723-34. ©2016 AACR.

摘要

去势抵抗性前列腺癌的蛋白质组学分析表明，约90%的患者中Src酪氨酸激酶活性增强。已知Src可诱导细胞周期蛋白D1，且细胞周期蛋白D1调控的基因表达模块可预测人类前列腺癌的不良预后。肿瘤相关钙信号转导蛋白2（TACSTD2/Trop2/M1S1）在前列腺中富集，通过γ-分泌酶切割复合物（PS1、PS2）和TACE（ADAM17）进行蛋白水解激活后可促进前列腺干细胞自我更新，从而释放Trop2细胞内结构域（Trop2 ICD）。在此，原代小鼠前列腺上皮细胞的v-Src转化增加了前列腺癌干细胞的比例，这通过基因表达、表位特征和前列腺球形成得以表征。v-Src诱导了细胞周期蛋白D1，且Src激酶诱导Trop2 ICD核积累需要细胞周期蛋白D1。细胞周期蛋白D1诱导了Trop2蛋白水解切割激活成分（PS2、TACE）的丰度，并抑制了Trop2蛋白水解复合物抑制成分（Numb）的表达。核Trop2 ICD和细胞周期蛋白D1增加而Numb减少的前列腺癌患者，其无复发生存概率降低（HR = 4.35）。因此，细胞周期蛋白D1通过增强Trop2蛋白水解激活复合物的丰度，作为v-Src介导的Trop2 ICD诱导的转导因子。《癌症研究》；76(22)；6723 - 34。©2016美国癌症研究协会。