ILK, PINCH and parvin: the tIPP of integrin signalling

Legate, Kyle R.; Montañez, Eloi; Kudlacek, Oliver; Fässler, Reinhard

doi:10.1038/nrm1789

Cited by 616 publications

(670 citation statements)

References 127 publications

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“…However, the mechanisms underlying this elevated ILK expression remained unclear. Previous studies showed that ILK expression can be upregulated by hypoxia (Abboud et al, 2007), inhibition of ubiquitin-mediated degradation through binding to PINCH (Legate et al, 2006) or peroxisome proliferator-activated receptor-mediated transcriptional repression (Yang et al, 2010). These data suggest that the cause of ILK upregulation may vary depending on tumor type.…”

Section: Discussionmentioning

confidence: 76%

“…ILK overexpression and deregulation are frequently observed in a wide variety of human cancers, further implicating ILK in tumorigenesis and cancer progression (Yoganathan et al, 2000;McDonald et al, 2008). Although it is known that ILK protein is stabilized through binding to PINCH (particularly interesting Cys-His-rich protein) (Legate et al, 2006) and that ILK transcription is regulated by peroxisome proliferator-activated receptor (Di-Poi et al, 2002;Yang et al, 2010), the mechanisms of ILK upregulation in cancer cells are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-mediated upregulation of integrin-linked kinase promotes Src-induced tumor progression

et al. 2011

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The tyrosine kinase c-Src is upregulated in various human cancers; however, the molecular mechanisms underlying c-Src-mediated tumor progression remain unclear. Here we show that downregulation of microRNA (miR)-542-3p is tightly associated with tumor progression via c-Src-related oncogenic pathways. In c-Src-transformed fibroblasts and human cancer cells that overexpress c-Src, miR-542-3p is substantially downregulated, and the ectopic expression of miR-542-3p suppresses tumor growth. We identified the integrin-linked kinase (ILK) as a conserved target of miR-542-3p. ILK upregulation promotes cell adhesion and invasion by activating the integrin-focal adhesion kinase (FAK)/c-Src pathway, and can also contribute to tumor growth via the AKT and glycogen synthase kinase 3b pathways. MiR-542-3p expression is downregulated by the activation of c-Src-related signaling molecules, including epidermal growth factor receptor, K-Ras and Ras/ Raf/mitogen-activated protein kinase/extracellular signalregulated kinase. In human colon cancer tissues, downregulation of miR-542-3p is significantly correlated with the upregulation of c-Src and ILK. Our results suggest that the novel c-Src-miR-542-3p-ILK-FAK circuit plays a crucial role in controlling tumor progression.

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Section: Discussionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

MicroRNA-mediated upregulation of integrin-linked kinase promotes Src-induced tumor progression

et al. 2011

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“…It is known that IPP members expression in physiological conditions controls normal development and tissue homeostasis. On the other hand, correlative studies of the three IPP members in cancer biology are still lacking and only the single components have been analysed 6,94 .…”

Section: The Ipp Complex (Ilk/pinch and Parvin) And Cancer Biologymentioning

confidence: 99%

Integrin signalling adaptors: not only figurants in the cancer story

et al. 2010

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Current evidence highlights the ability of adaptor (or scaffold) proteins to create signalling platforms that drive cellular transformation upon integrin-dependent adhesion and growth factor receptor activation. The understanding of the biological effects regulated by these adaptors in tumours might be crucial for the identification of novel targets and the development of innovative therapeutic strategies for human cancer. In this review we will discuss the relevance of adaptor proteins in signalling originating from integrin-mediated cell-extracellular matrix (ECM) adhesion and growth factor stimulation within the context of cell transformation and tumour progression.Herein, we will specifically underline the contribution of p130CAS, NEDD9, CRK, and the IPP complex (ILK, PINCH and PARVIN) to cancer, along with the more recently identified p140CAP.

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“…Eighteen a and eight b subunits congregate to form 24 different a/b heterodimers dependent on cell type and cellular context (Hynes, 2002). Similar to soluble growth factors and cytokines, integrin-mediated signaling regulates survival, proliferation and differentiation (Giancotti and Ruoslahti, 1999;Legate et al, 2006). Because integrins lack own kinase activity, cytoplasmic protein kinases such as integrin-linked kinase (ILK) (Hannigan et al, 1996) or the non-receptor-bound focal adhesion kinase (FAK) (Mitra et al, 2005) or Rho GTPases like Rac and Cdc42 (Kinbara et al, 2003) are recruited by integrins to transmit signals to intracellular pathways.…”

Section: Introductionmentioning

confidence: 99%

Integrin-linked kinase interacts with caspase-9 and -8 in an adhesion-dependent manner for promoting radiation-induced apoptosis in human leukemia cells

et al. 2006

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Integrin-mediated adhesion of leukemia cells to extracellular matrix proteins reduces apoptosis following radiation-induced genotoxic injury. To evaluate the role of integrin-linked kinase (ILK) in this process, HL60 human acute promyelocytic leukemia cells were stably transfected with ILK wild-type or kinase-hyperactive overexpression vectors. Suspension or fibronectin (FN) adhesion cultures were irradiated with X-rays and processed for measurement of apoptosis, mitochondrial transmembrane potential and caspase activation. Adhesion to FN pronouncedly reduced radiation-induced apoptosis of HL60 cells and vector controls. Intriguingly, overexpressed ILK enhanced apoptosis after irradiation by combined activation of caspase-3 through caspase-8 and -9 in irradiated FN cultures. Irradiation of ILK suspension cultures lacked caspase-8 activation, but showed serial cleavage of caspase-9, -3 and poly (ADPribose) polymerase. These findings further characterize the cell death-promoting function of ILK in DNAdamaged cells. Moreover, ILK might represent a potential therapeutic target for innovative chemo-and radiooncological approaches in hematological malignancies.

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ILK, PINCH and parvin: the tIPP of integrin signalling

Cited by 616 publications

References 127 publications

MicroRNA-mediated upregulation of integrin-linked kinase promotes Src-induced tumor progression

MicroRNA-mediated upregulation of integrin-linked kinase promotes Src-induced tumor progression

Integrin signalling adaptors: not only figurants in the cancer story

Integrin-linked kinase interacts with caspase-9 and -8 in an adhesion-dependent manner for promoting radiation-induced apoptosis in human leukemia cells

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