Kindlin-2 promotes genome instability in breast cancer cells

Zhao, Ting; Guan, Lina; Yu, Yu; Pei, Xuelian; Zhan, Jun; Han, Leng; Tang, Yan; Li, Feng; Fang, Wei; Zhang, Hongquan

doi:10.1016/j.canlet.2012.11.043

Cited by 35 publications

(33 citation statements)

References 42 publications

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“…FERMT2 can stimulate genomic instability, which ultimately facilitates breast cancer progression, and it also has been identified as a binding partner for KIND1, mutations in which are responsible for Kindler syndrome [99, 100]. Shulman et al [46] independently validated the recent association of FERMT2 with LOAD risk after performing a gene screen and in vivo studies in Drosophila melanogaster .…”

Section: Identification Of Load Genes By Genome-wide Association Studiesmentioning

confidence: 99%

Late-Onset Alzheimer’s Disease Genes and the Potentially Implicated Pathways

2014

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Late-onset Alzheimer’s disease (LOAD) is a devastating neurodegenerative disease with no effective treatment or cure. In addition to APOE, recent large genome-wide association studies have identified variation in over 20 loci that contribute to disease risk: CR1, BIN1, INPP5D, MEF2C, TREM2, CD2AP, HLA-DRB1/HLA-DRB5, EPHA1, NME8, ZCWPW1, CLU, PTK2B, PICALM, SORL1, CELF1, MS4A4/MS4A6E, SLC24A4/RIN3,FERMT2, CD33, ABCA7, CASS4. In addition, rare variants associated with LOAD have also been identified in APP, TREM2 and PLD3 genes. Previous research has identified inflammatory response, lipid metabolism and homeostasis, and endocytosis as the likely modes through which these gene products participate in Alzheimer’s disease. Despite the clustering of these genes across a few common pathways, many of their roles in disease pathogenesis have yet to be determined. In this review, we examine both general and postulated disease functions of these genes and consider a comprehensive view of their potential roles in LOAD risk.

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Section: Identification Of Load Genes By Genome-wide Association Studiesmentioning

confidence: 99%

Late-Onset Alzheimer’s Disease Genes and the Potentially Implicated Pathways

2014

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“…The F2 subdomain is bisected by a pleckstrin homology (PH) domain [3] . Functionally, mig-2 is a significant regulator of integrin activation and cell-extracellular matrix (ECM) adhesion [4] , and it is related to carcinogenesis and tumor progression in breast cancer, gastric cancer and prostate cancer [5][6][7] . However, the function of mig-2 in regulating glioma tumorigenesis has not been reported.…”

Section: Introductionmentioning

confidence: 99%

Mig-2 attenuates cisplatin-induced apoptosis of human glioma cells in vitro through AKT/JNK and AKT/p38 signaling pathways

Ou¹,

Zhao

et al. 2014

Acta Pharmacol Sin

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Aim: Mig-2 (also known as Kindlin-2 and FERMT2) is an important regulator of integrin activation and cell-extracellular matrix adhesion, and involved in carcinogenesis and tumor progression. The aim of this study was to investigate the role of mig-2 in cisplatin-induced apoptosis of human glioma cells in vitro. Methods: The expression of mig-2 was modulated in human glioma H4, HS 683 and U-87 MG cells by transfection with a plasmid carrying mig-2 or mig-2 siRNA. Cisplatin-induced apoptosis was detected using Annexin V/PI staining and flow cytometry, as well as MTS analyses. The expression of apoptosis-related or signaling proteins was examined using Western blotting analysis. H4 cells were transfected with plasmids carrying mig-2 mutants to determine the functional domain of mig-2. Results: In the 3 glioma cell lines tested, overexpression of mig-2 significantly attenuated cisplatin-induced apoptosis, whereas knockdown of mig-2 potentiated the apoptosis. The mechanisms of action of mig-2 were further addressed in H4 cells: overexpression of mig-2 markedly reduced cleaved caspase-9, caspase-8, caspase-3 and PARP, as well as p-JNK and p-p38, and increased p-AKT in cisplatin-treated H4 cells, whereas mig-2 siRNA reversely changed these apoptosis-related and signaling proteins. Furthermore, pretreatment with JNK inhibitor SP600125 and p38 inhibitor SB203580, or with AKT inhibitor LY294002 abolished the effects of mig-2 on cisplaxtin-induced apoptosis. In H4 cells, GFP-mig-2 F3 plasmid that contained only the F3 subdomain showed the same efficiency in attenuating cisplatin-induced apoptosis, as the mig-2 wild-type vector did, whereas GFP-mig-2 (1-541) plasmid that lacked the F3 subdomain was inactive. Conclusion: Mig-2 significantly attenuates the antitumor action of cisplatin against human glioma cells in vitro through AKT/JNK and AKT/p38 signaling pathways. The F3 subdomain of mig-2 is necessary and sufficient for this effect.

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“…In addition to regulation of EMT and invasion, kindlin-2 has been shown to promote cell survival through stimulation of Hedgehog signaling by inducing the expression of Loss of expression increases cell invasion EMMPRIN regulates kindlin-3 and β1 integrin expression Delyon et al, 2015 Gli1 and anti-apoptotic Bcl2 proteins (Gao et al, 2013;Gong et al, 2010;Shen et al, 2013). Kindlin-2 has also suggested to enhance genome instability, a hallmark of cancer formation, although it is not clear how this is achieved at the molecular level (Zhao et al, 2013). It has also been reported that, in mesenchymal tumor cells, high kindlin-2 levels suppress invasion through inhibition of urokinasetype plasminogen activator (uPA) secretion (Shi and Wu, 2008) and impair tumor progression of serous epithelial ovarian cancer through up-regulation of estrogen receptors, which leads to mesenchymal-toepithelial transition (MET) and, as a consequence, to reduced tumor cell dissemination (Ren et al, 2014).…”

Section: Kindlin-2 Is Involved In Multiple Diseasesmentioning

confidence: 99%

The kindlin family: functions, signaling properties and implications for human disease

Rognoni

Ruppert

Fässler

2016

Journal of Cell Science

189

186

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The kindlin (or fermitin) family of proteins comprises three members (kindlin-1,-2 and -3) of evolutionarily conserved focal adhesion (FA) proteins, whose best-known task is to increase integrin affinity for a ligand (also referred as integrin activation) through binding of β-integrin tails. The consequence of kindlin-mediated integrin activation and integrin-ligand binding is cell adhesion, spreading and migration, assembly of the extracellular matrix (ECM), cell survival, proliferation and differentiation.

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Kindlin-2 promotes genome instability in breast cancer cells

Cited by 35 publications

References 42 publications

Late-Onset Alzheimer’s Disease Genes and the Potentially Implicated Pathways

Late-Onset Alzheimer’s Disease Genes and the Potentially Implicated Pathways

Mig-2 attenuates cisplatin-induced apoptosis of human glioma cells in vitro through AKT/JNK and AKT/p38 signaling pathways

The kindlin family: functions, signaling properties and implications for human disease

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