β-parvin inhibits integrin-linked kinase signaling and is downregulated in breast cancer

Mongroo, Perry S.; Johnstone, Cameron N.; Naruszewicz, Izabela; Leung-Hagesteijn, Chungyee; Sung, Raphael K.; Carnio, Leanne; Rustgi, Anil K.; Hannigan, Gregory E.

doi:10.1038/sj.onc.1208112

Cited by 65 publications

(75 citation statements)

References 55 publications

(61 reference statements)

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“…PARVB (which encodes PARVIN ) mRNA and protein levels are markedly downregulated in a number of advanced breast tumours 36 and its expression is inversely correlated with ILK protein and kinase activity levels, suggesting that down-regulation of PARVB expression upregulates ILK activity in human tumours (Table 1). Regarding PINCH1/2 expression in samples of breast, prostate, lung, colon, and skin carcinomas, both proteins have been found to be upregulated in tumour-associated stromal cells, especially at the tumour invasive edges 37 .…”

Section: Integrin Adaptors In Cancermentioning

confidence: 99%

“…Recently, a new function of ILK in the regulation of the microtubule cytoskeleton and mitotic spindle organization has been proposed 103 High levels of PARVIN correlate with increased cell adhesion, induce reversal of anchorageindependent growth 36 , and attenuation of tumour growth in nude mice 110 . The latter tumoursuppressive role of PARVIN is consistent with deletions observed in its locus (22q13.21) in some colon and breast cancer cells 111 .…”

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

confidence: 99%

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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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Section: Integrin Adaptors In Cancermentioning

confidence: 99%

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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“…It has also been shown that actopaxin (␣-parvin) and affixin (␤-parvin) compete for ILK binding (42). These interactions exert opposing effects on ILK kinase activity (25,43). Due to the negative regulation of TESK1 activity by actopaxin reported herein, it will be important to determine whether ␤-parvin binds TESK1 and if so how this may affect its activity.…”

Section: Fig 11mentioning

confidence: 99%

Actopaxin Interacts with TESK1 to Regulate Cell Spreading on Fibronectin

LaLonde

Brown

Bouverat

et al. 2005

Journal of Biological Chemistry

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The focal adhesion protein actopaxin contributes to integrin-actin associations and is involved in cell adhesion, spreading, and motility. Herein, we identify and characterize an association between actopaxin and the serine/threonine kinase testicular protein kinase 1 (TESK1), a ubiquitously expressed protein previously reported to regulate cellular spreading and focal adhesion formation via phosphorylation of cofilin. The interaction between actopaxin and TESK1 is direct and the binding sites were mapped to the carboxyl terminus of both proteins. The association between actopaxin and TESK1 is negatively regulated by adhesion to fibronectin, and a phosphomimetic actopaxin mutant that promotes cell spreading also exhibits impaired binding to TESK1. Binding of actopaxin to TESK1 inhibits TESK1 kinase activity in vitro. Expression of the carboxyl terminus of actopaxin has previously been reported to retard cell spreading. This effect was reversed following overexpression of TESK1 and was found to be dependent on an inability of actopaxin carboxyl terminus expressing cells to promote cofilin phosphorylation upon matrix adhesion and caused by retention of TESK1 by this actopaxin mutant. Thus, the association between actopaxin and TESK1, which is likely regulated by phosphorylation of actopaxin, regulates TESK1 activity and subsequent cellular spreading on fibronectin.Integrin-mediated adhesion to the extracellular matrix (ECM) 1 leads to extensive actin reorganization that is regulated predominantly by the Rho family of GTPases, Cdc42, Rac, and Rho, to stimulate formation of the actin-dependent structures filopodia, lamellipodia, and stress fibers, respectively (1). Activated Rho family members interact with numerous effectors, including the p21-associated kinase (PAK), the WiskottAldrich Syndrome protein (WASP), and the Rho-associated kinase (ROCK). PAK and ROCK share some common target proteins, including the LIM kinases (LIMK) (1). Closely related to the LIM family of kinases are TESK1 and TESK2 (testicular protein kinases), which were originally identified in testicular cells but have since been found to be ubiquitously expressed (2-5). Unlike LIMK, regulation of TESK1 activity by Rho GTPases has not been confirmed, although recent studies in Drosophila implicate a role in the Rac pathway associated with both eye development and spermatogenesis (6). However, this kinase has been shown to be activated upon matrix adhesion and is regulated by binding of 8).TESK1, as is the case with LIMK, regulates integrin-dependent focal adhesion assembly and actin organization through phosphorylation of the amino terminus of the F-actin-severing protein cofilin (3). Phosphorylation on serine 3, which is reversed by the serine phosphatases slingshot and chronophin, has been shown to decrease cofilin activity by interfering with its ability to bind F-actin (9 -11). Cofilin is a critical regulator of both growth factor and matrix-dependent actin reorganization, affecting lamellipodia formation, cell spreading, motility, and polarit...

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“…ILK modulates integrinmediated adhesion by directly interacting with the cytoplasmic tails of b1-or b3-integrin receptors (Hannigan et al, 1996), and complexes with Parvin A/B (Attwell et al, 2003;Mongroo et al, 2004) and PINCH (Tu et al, 1999). More recently, ILK has also been shown to have an instrumental role in the proper organization of the mitotic spindle during cell division (Fielding et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Integrin-linked kinase has a critical role in ErbB2 mammary tumor progression: implications for human breast cancer

et al. 2010

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Elevated expression of the integrin-linked kinase (ILK) has been observed in a variety of cancers and has been further correlated with poor clinical outcome. Here, we show that mammary epithelial disruption of ILK results in a profound block in mammary tumor induction. Consistent with these observations, inhibition of ILK function in ErbB2-expressing cells with small molecule inhibitor or RNA interference resulted in profound block in their in vitro invasive properties due to the induction of apoptotic cell death. The rare ILK-deficient tumors that eventually arose overcame this block in tumor induction by an upregulation of ErB3 phosphorylation. These observations provide direct evidence that ILK has a critical role in the initiation phase of ErbB2 tumor induction.

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β-parvin inhibits integrin-linked kinase signaling and is downregulated in breast cancer

Cited by 65 publications

References 55 publications

Integrin signalling adaptors: not only figurants in the cancer story

Integrin signalling adaptors: not only figurants in the cancer story

Actopaxin Interacts with TESK1 to Regulate Cell Spreading on Fibronectin

Integrin-linked kinase has a critical role in ErbB2 mammary tumor progression: implications for human breast cancer

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