Regulation of hemidesmosome disassembly by growth factor receptors

Margadant, Coert; Frijns, Evelyne; Wilhelmsen, Kevin; Sonnenberg, Arnoud

doi:10.1016/j.ceb.2008.05.001

Cited by 104 publications

(104 citation statements)

References 51 publications

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“…6 integrin forms a heterodimer with 4 subunit and functions as a surface receptor for laminin-332 (Margadant et al, 2008). We confirmed the polarized expression of 64 integrin (Marchisio et al, 1991) at the basal surface of keratinocytes (Fig.…”

Section: 64 Integrin Is Required For Collective Motionsupporting

confidence: 70%

Cell motion predicts human epidermal stemness

Nanba¹,

Toki²,

Tate³

et al. 2015

J Exp Med

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Section: 64 Integrin Is Required For Collective Motionsupporting

confidence: 70%

Cell motion predicts human epidermal stemness

Nanba¹,

Toki²,

Tate³

et al. 2015

J Exp Med

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“…Several protein kinases can phosphorylate b4-integrin, including PKC, PKA, the Epidermal Growth Factor Receptor, and the Macrophage Stimulating Factor Receptor (Santoro et al, 2003;Rabinovitz et al, 2004;Wilhelmsen et al, 2007). However, controversy remains in explaining their roles in hemidesmosome formation due to unphysiological experimental conditions (Margadant et al, 2008).…”

Section: Post-translational Modificationmentioning

confidence: 99%

The making of hemidesmosome structures in vivo

Zhang

Labouesse

2010

Developmental Dynamics

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Hemidesmosomes are evolutionarily conserved attachment complexes linked to intermediate filaments that connect epithelial cells to the extracellular matrix. They provide tissue integrity and resistance to mechanical forces. Alterations in hemidesmosome structures are responsible for skin blistering, carcinoma invasion, and wound-healing defects. Valuable information about hemidesmosome assembly and disassembly has been obtained from in vitro cell culture studies. However, how these processes take place in vivo still remains elusive. Here, we discuss recent data about the formation and reorganization of hemidesmosomes in several in vivo model systems, particularly zebrafish and Caenorhabditis elegans, focusing on various factors affecting their dynamics. Mechanisms found in different organisms reveal that hemidesmosome formation and maintenance in vivo are carefully controlled by ECM protein folding, ECM-receptor expression and trafficking, and by post-translational modification of hemidesmosome components. These findings validate and extend the in vitro studies, and shed light on our understanding about hemidesmosomes across species.

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“…In addition, ITGB4 has a potential role in signaling events associated with migration, cell growth, and survival under physiological and pathological conditions. [9][10][11] Prior reports indicate that ITGB4 is upregulated in multiple tumor types, including pancreatic cancer. 8 In several cancers, high levels of ITGB4 expression have been linked to poor prognosis or aggressive behavior, [12][13][14][15][16] but the clinicopathological significance of ITGB4 overexpression in PDA remains unclear.…”

mentioning

confidence: 99%

Upregulation of integrin β4 promotes epithelial–mesenchymal transition and is a novel prognostic marker in pancreatic ductal adenocarcinoma

Masugi

Yamazaki

Emoto

et al. 2015

Laboratory Investigation

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Pancreatic ductal adenocarcinoma (PDA) is a highly aggressive and often lethal malignant tumor. Several studies have shown that epithelial-mesenchymal transition (EMT) is frequently observed in clinical samples of PDA and is related to high metastatic rates and poor outcomes. To identify candidate molecules regulating EMT in PDA, we previously used cDNA microarray analysis and identified integrin b4 (ITGB4) as one of the genes upregulated in high-EMT xenografts derived from PDA patients. The aim of the current study was to clarify the clinicopathological and functional significance of ITGB4 overexpression in PDA. ITGB4 upregulation in high-EMT xenografts was confirmed by immunohistochemistry. Immunohistochemical analyses of 134 surgically resected PDA cases revealed intratumoral heterogeneity with respect to ITGB4 expression and showed that cancer cells undergoing EMT often display strong diffuse ITGB4 expression. High levels of ITGB4 expression were significantly correlated with the hallmarks of EMT (solitary cell infiltration, reduced E-cadherin expression, and increased vimentin expression), with high tumor grade, and with the presence of lymph node metastasis, and showed an independent prognostic effect. Immunocytochemical analyses of PDA cell lines revealed that localization of ITGB4 changed from regions of cell-cell contact to diffuse cytoplasm and cell edges with occasional localization in filopodia during EMT. Knockdown of ITGB4 reduced the migratory and invasive ability of PDA cells. Overexpression of ITGB4 promoted cell scattering and cell motility in combination with downregulation of E-cadherin and upregulation of vimentin expression. In conclusion, we elucidated the prognostic and clinicopathological significance of ITGB4 overexpression in PDA and also the potential role for ITGB4 in the regulation of cancer invasion and EMT. Pancreatic cancer is the fourth most common cause of cancer death in men and women in the United States. 1 Despite medical improvements, pancreatic cancer remains one of the most lethal malignancies: the 5-year survival rate for patients with pancreatic cancer is only about 6%. 1 Pancreatic ductal adenocarcinoma (PDA), characterized by the formation of ducts resembling pancreatic ducts, is the most common histologic type of pancreatic cancer. Resectability is considered to be the most significant prognostic factor; however, at the time of diagnosis, only about 20% of patients with PDA are surgically resectable because of distant metastases or major vessel involvement. 2 Even after curative surgery, the 5-year survival rate is 10%-25%, mainly due to the highly aggressive biological behavior of this tumor, such as the high rate of local recurrence, peritoneal dissemination, liver metastases, and lymph node recurrence. 3 The epithelial-mesenchymal transition (EMT) is a series of cellular and molecular processes during which polarized epithelial cells lose cell-cell and cell-basement membrane interactions at the same time as acquiring mesenchymal and migratory properties. EMT is no...

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Regulation of hemidesmosome disassembly by growth factor receptors

Cited by 104 publications

References 51 publications

Cell motion predicts human epidermal stemness

Cell motion predicts human epidermal stemness

The making of hemidesmosome structures in vivo

Upregulation of integrin β4 promotes epithelial–mesenchymal transition and is a novel prognostic marker in pancreatic ductal adenocarcinoma

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