Suppr超能文献

与CXCL12/CXCR4介导的细胞增殖相关的信号传导机制依赖于PTEN。

Signaling mechanisms coupled to CXCL12/CXCR4-mediated cellular proliferation are PTEN-dependent.

作者信息

Begley Lesa A, Kasina Sathish, Shah Rajal B, Macoska Jill A

机构信息

Section of General Surgery, University of Michigan Ann Arbor, MI.

MMS Holdings, Inc. Canton, MI.

出版信息

Am J Clin Exp Urol. 2015 Aug 8;3(2):91-9. eCollection 2015.

Abstract

A key difference between normal and malignant prostate cells in vitro and in vivo is that both alleles of PTEN are largely intact in normal benign prostate glands and cultured epithelial cells, whereas one or both alleles of PTEN are mutant or deleted in the majority of prostate tumors and malignant prostate cancer cell lines. Intact PTEN suppresses phosphorylation of Akt downstream of PI3K activation in non-transformed cells whereas Akt phosphorylation is unimpeded in malignant cells that are often PTEN-deficient. We have previously shown that activation of the CXCL12/CXCR4 axis transactivates the EGFR to promote pro-proliferative signaling preferentially through the Raf/MEK/Erk pathway in benign prostate epithelial cells. These cells demonstrate little basal pAkt and these levels do not increase with CXCL12 stimulation because PTEN is intact and fully functional. Thus, inactivation of PTEN may be the critical factor that modulates downstream signaling and the specific CXCL12-stimulated proliferative responses of non-transformed and transformed prostate epithelial cells. Based on these data, we hypothesize that the CXCL12/CXCR4-mediated activation of downstream pro-proliferative signaling through the Raf/MEK/Erk or PI3K/Akt pathways is modulated by PTEN status.

摘要

体外和体内正常前列腺细胞与恶性前列腺细胞之间的一个关键差异在于,在正常良性前列腺腺体和培养的上皮细胞中,PTEN的两个等位基因基本完整,而在大多数前列腺肿瘤和恶性前列腺癌细胞系中,PTEN的一个或两个等位基因发生突变或缺失。完整的PTEN可抑制非转化细胞中PI3K激活下游的Akt磷酸化,而在通常缺乏PTEN的恶性细胞中,Akt磷酸化不受阻碍。我们之前已经表明,CXCL12/CXCR4轴的激活可反式激活EGFR,从而优先通过Raf/MEK/Erk途径促进良性前列腺上皮细胞中的促增殖信号传导。这些细胞几乎没有基础pAkt,并且由于PTEN完整且功能正常,这些水平不会随着CXCL12刺激而增加。因此,PTEN的失活可能是调节下游信号传导以及非转化和转化前列腺上皮细胞对CXCL12特异性刺激的增殖反应的关键因素。基于这些数据,我们假设CXCL12/CXCR4通过Raf/MEK/Erk或PI3K/Akt途径介导的下游促增殖信号传导的激活受PTEN状态的调节。

相似文献

2
Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance.
Adv Enzyme Regul. 2006;46:249-79. doi: 10.1016/j.advenzreg.2006.01.004. Epub 2006 Jul 18.
3
CXCL12/CXCR4 Axis Activation Mediates Prostate Myofibroblast Phenoconversion through Non-Canonical EGFR/MEK/ERK Signaling.
PLoS One. 2016 Jul 19;11(7):e0159490. doi: 10.1371/journal.pone.0159490. eCollection 2016.
5
CXCL12/SDF-1α induces migration via SRC-mediated CXCR4-EGFR cross-talk in gastric cancer cells.
Oncol Lett. 2017 Aug;14(2):2103-2110. doi: 10.3892/ol.2017.6389. Epub 2017 Jun 15.
7
Proinflammatory CXCL12-CXCR4/CXCR7 Signaling Axis Drives Myc-Induced Prostate Cancer in Obese Mice.
Cancer Res. 2017 Sep 15;77(18):5158-5168. doi: 10.1158/0008-5472.CAN-17-0284. Epub 2017 Jul 7.
9
Contributions of the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways to leukemia.
Leukemia. 2008 Apr;22(4):686-707. doi: 10.1038/leu.2008.26. Epub 2008 Mar 13.

引用本文的文献

1
Clinicopathological Evaluation of Papillary Thyroid Microcarcinoma.
Cureus. 2024 Mar 18;16(3):e56404. doi: 10.7759/cureus.56404. eCollection 2024 Mar.
2
[MiR-30e-5p overexpression promotes proliferation and migration of colorectal cancer cells by activating the CXCL12 axis downregulating PTEN].
Nan Fang Yi Ke Da Xue Xue Bao. 2023 Jul 20;43(7):1081-1092. doi: 10.12122/j.issn.1673-4254.2023.07.04.
5
Post-Translational Modifications That Drive Prostate Cancer Progression.
Biomolecules. 2021 Feb 9;11(2):247. doi: 10.3390/biom11020247.

本文引用的文献

1
Unexpected low-dose toxicity of the universal solvent DMSO.
FASEB J. 2014 Mar;28(3):1317-30. doi: 10.1096/fj.13-235440. Epub 2013 Dec 10.
2
ADAM-mediated amphiregulin shedding and EGFR transactivation.
Cell Prolif. 2009 Dec;42(6):799-812. doi: 10.1111/j.1365-2184.2009.00645.x. Epub 2009 Sep 7.
3
Interactions between cells with distinct mutations in c-MYC and Pten in prostate cancer.
PLoS Genet. 2009 Jul;5(7):e1000542. doi: 10.1371/journal.pgen.1000542. Epub 2009 Jul 3.
4
The inflammatory microenvironment of the aging prostate facilitates cellular proliferation and hypertrophy.
Cytokine. 2008 Aug;43(2):194-9. doi: 10.1016/j.cyto.2008.05.012. Epub 2008 Jun 24.
5
CXCL12 activates a robust transcriptional response in human prostate epithelial cells.
J Biol Chem. 2007 Sep 14;282(37):26767-26774. doi: 10.1074/jbc.M700440200. Epub 2007 Jul 12.
6
Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance.
Biochim Biophys Acta. 2007 Aug;1773(8):1263-84. doi: 10.1016/j.bbamcr.2006.10.001. Epub 2006 Oct 7.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验