Alterations of Collagen XVII Expression During Transformation of Oral Epithelium to Dysplasia and Carcinoma

Parikka, Mataleena; Kainulainen, Tiina; Tasanen, Kaisa; Väänänen, Antti; Bruckner‐Tuderman, Leena; Salo, Tuula

doi:10.1177/002215540305100707

Cited by 49 publications

(62 citation statements)

References 32 publications

(47 reference statements)

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“…Here, we have provided evidence that Col XVII, by mediating the association of BPAG1e and ␣6␤4 integrin, is an important regulator of the keratinocyte lamellipodium, the key organelle that generates the force necessary for directional protrusion at the cell periphery (49,53). Thus, our results now provide a critical new understanding of the consequences of up-regulation of Col XVII, ␣6␤4 integrin, and BPAG1e in aggressive tumors and the presence of these proteins at the leading front of migrating tumor and epidermal cells covering wounds (17,20,(42)(43)(44)(45). They are clearly key players in the regulation of motility.…”

Section: Discussionsupporting

confidence: 54%

“…For example, we and others have demonstrated that ␣6␤4 integrin is directly involved in regulating signals that control motile phenomena (16,18,19,21,41). Moreover, the up-regulation of ␣6␤4 integrin, BPAG1e, and Col XVII in aggressive tumor cells, their presence in lamellipodia in cultured cells, and the observation that they are found in the leading edge of cells populating wounds point to a more direct role in migration (17,20,(42)(43)(44)(45).…”

Section: Discussionmentioning

confidence: 85%

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Type XVII Collagen Regulates Lamellipod Stability, Cell Motility, and Signaling to Rac1 by Targeting Bullous Pemphigoid Antigen 1e to α6β4 Integrin

Hamill

Hopkinson

Jonkman

et al. 2011

Journal of Biological Chemistry

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Rac1 activity, polarity, lamellipodial dynamics, and directed motility are defective in keratinocytes exhibiting deficiency in ␤4 integrin or knockdown of the plakin protein Bullous Pemphigoid Antigen 1e (BPAG1e). The activity of Rac, formation of stable lamellipodia, and directed migration are restored in ␤4 integrin-deficient cells by inducing expression of a truncated form of ␤4 integrin, which lacks binding sites for BPAG1e and plectin. In these same cells, BPAG1e, the truncated ␤4 integrin, and type XVII collagen (Col XVII), a transmembrane BPAG1e-binding protein, but not plectin, colocalize along the substratum-attached surface. This finding suggested to us that Col XVII mediates the association of BPAG1e and ␣6␤4 integrin containing the truncated ␤4 subunit and supports directed migration. To test these possibilities, we knocked down Col XVII expression in keratinocytes expressing both full-length and truncated ␤4 integrin proteins. Col XVII-knockdown keratinocytes exhibit a loss in BPAG1e-␣6␤4 integrin interaction, a reduction in lamellipodial stability, an impairment in directional motility, and a decrease in Rac1 activity. These defects are rescued by a mutant Col XVII protein truncated at its carboxyl terminus. In summary, our results suggest that in motile cells Col XVII recruits BPAG1e to ␣6␤4 integrin and is necessary for activation of signaling pathways, motile behavior, and lamellipodial stability.Re-epithelialization, the process by which epidermal cells undergo directed migration and move over an exposed wound bed, is a critical aspect in the closure of epithelial wounds. Factors that impact the ability of a cell to migrate can be roughly grouped into those involved in the basic mechanism of motility and those involved in the steering mechanism (1). To migrate efficiently, in a directed manner, cells must establish and maintain an asymmetric morphology with defined leading and trailing edges (2). This leading edge is characterized by a sheet-like extension termed a lamellipodium (1). Moreover, the rates of extension, the stability of the formed lamellipodium, and the size of the extension are the determining factors in defining the migration characteristics of a cell (3, 4). Indeed, the rate of lamellipodium extension correlates with migration rate, whereas lamellipodium stability (persistence) correlates with processivity or turning frequency (1).Lamellipodium formation requires localized rearrangement of the actin cytoskeleton, which involves signaling mediated by Rac1 (a small GTPase of the Rho family) to the actin severing protein cofilin (5). Through severing of actin filaments, cofilin increases the number of free actin barbed ends from which actin filaments extend while simultaneously increasing the depolymerization rate of older actin filaments, thereby increasing the local pool of free actin monomers (6). Spatial control of Rac1 and cofilin activity can therefore drive localized extension of the actin-rich lamellipodium. In addition to rearrangement of the actin cytoskeleton, lamellipo...

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 85%

Type XVII Collagen Regulates Lamellipod Stability, Cell Motility, and Signaling to Rac1 by Targeting Bullous Pemphigoid Antigen 1e to α6β4 Integrin

Hamill

Hopkinson

Jonkman

et al. 2011

Journal of Biological Chemistry

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“…Collagen XVII is mutated in epidermolysis bullosa, is a serum antigen in a number of skin blistering conditions (reviewed in ref. 26), and is up-regulated in oral and squamous basal cell carcinomas (27,28). Collagen XIII is a serum antigen in the autoimmune disease, Graves' ophthalmopathy (29), and was recently reported to be up-regulated in mesenchymal tumors and in the stroma of epithelial tumors (30), whereas collagen XXV is deposited in Alzheimer's plaques (31).…”

Section: Discussionmentioning

confidence: 99%

Collagen XXIII Expression Is Associated with Prostate Cancer Recurrence and Distant Metastases

Banyard

Bao

Hofer

et al. 2007

Clinical Cancer Research

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Purpose: We had previously identified a new transmembrane collagen, type XXIII, in metastatic rat prostate carcinoma cells. The purpose of this study was to determine the expression of collagen XXIII in human prostate cancer and investigate its relationship with disease progression. Experimental Design: We investigated collagen XXIII expression in prostate cancer tissue and did a retrospective analysis of association with prostate-specific antigen (PSA)^defined disease recurrence. The presence of collagen XXIII in prostate cancer patient urine was also assessed before and after prostatectomy. Results: Collagen XXIII protein was detected at very low levels in benign prostate tissue and was significantly increased in prostate cancer. Distant metastases exhibited significantly higher collagen XXIII levels compared with either localized prostate cancer or regional (lymph node) metastases. Patients with high collagen XXIII levels had a 2.8-fold higher risk of PSA failure with median time to failure of 8.1 months, compared with low collagen XXIII patients with a median time to failure of 5 years. Multivariate Cox regression showed that the presence of collagen XXIII was significantly associated with time to PSA recurrence, independent of other clinical variables. Collagen XXIII was also detected in prostate cancer patient urine, with reduced levels after prostatectomy, indicating potential as a noninvasive fluid biomarker. Conclusions: We present the first report demonstrating increased collagen XXIII expression in prostate cancer tissue.We show that collagen XXIII level is a significant independent predictor of PSA-defined disease recurrence, suggesting a potential role as a molecular biomarker of prostate cancer progression and metastasis.

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“…In light of this, the evidence that altered expression of desmosomal proteins in various human malignancies has been accumulating. [175].…”

Section: Malignancy In Relation To the Autoimmunity In Pemphigus Groumentioning

confidence: 99%

Malignancy in Relation to Autoimmune Blistering Dermatoses: Molecular and Clinical Aspects

Pietkiewicz¹,

Gornowicz‐Porowska²,

Dmochowska³

et al. 2013

Highlights in Skin Cancer

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Alterations of Collagen XVII Expression During Transformation of Oral Epithelium to Dysplasia and Carcinoma

Cited by 49 publications

References 32 publications

Type XVII Collagen Regulates Lamellipod Stability, Cell Motility, and Signaling to Rac1 by Targeting Bullous Pemphigoid Antigen 1e to α6β4 Integrin

Type XVII Collagen Regulates Lamellipod Stability, Cell Motility, and Signaling to Rac1 by Targeting Bullous Pemphigoid Antigen 1e to α6β4 Integrin

Collagen XXIII Expression Is Associated with Prostate Cancer Recurrence and Distant Metastases

Malignancy in Relation to Autoimmune Blistering Dermatoses: Molecular and Clinical Aspects

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