Integrins in thyroid tissue: upregulation of alpha2beta1 in anaplastic thyroid carcinoma

Dahlman, T; Grimelius, Lars; Wallin, Göran; Rubin, Kristofer; Westermark, Kerstin

doi:10.1530/eje.0.1380104

Cited by 26 publications

(20 citation statements)

References 53 publications

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“…Similar findings have been reported using flow cytofluorometry, where expression of integrins such as α1β1 and α6β1 was found in normal thyroid and tumor specimens, integrin α6β4 expression was found only in thyroid carcinomas and carcinoma cell lines (111). Others have confirmed neoexpression of integrin α6β4 in thyroid carcinoma tissue (112, 113) and have also found that it is expressed in anaplastic thyroid carcinoma, an aggressive and poorly differentiated malignancy (112). …”

Section: Malignancies With Strong Evidence That Integrin β4 Expressiomentioning

confidence: 85%

Clinical significance of the integrin α6β4 in human malignancies

Stewart

O’Connor

2015

Laboratory Investigation

182

181

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Integrin α6β4 is a cellular adhesion molecule that binds to laminins in the extracellular matrix and nucleates the formation of hemidesmosomes. During carcinoma progression, integrin α6β4 is released from hemidesmosomes, where it can then signal to facilitate multiple aspects of tumor progression including sustaining proliferative signaling, tumor invasion and metastasis, evasion of apoptosis, and stimulation of angiogenesis. The integrin achieves these ends by cooperating with growth factor receptors including EGFR, ErbB-2, and c-Met to amplify downstream pathways such as PI3K, AKT, MAPK and the Rho family small GTPases. Furthermore, it dramatically alters the transcriptome toward a more invasive phenotype by controlling promoter DNA demethylation of invasion and metastasis-associated proteins, such as S100A4 and autotaxin, and upregulates and activates key tumor promoting transcription factors such as the NFATs and NFkB. Expression of integrin α6β4 has been studied in many human malignancies where its overexpression is associated with aggressive behavior and a poor prognosis. This review provides an assessment of integrin α6β4 expression patterns and their prognostic significance in human malignancies, and describes key signaling functions of integrin α6β4 that contribute to tumor progression.

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Section: Malignancies With Strong Evidence That Integrin β4 Expressiomentioning

confidence: 85%

Clinical significance of the integrin α6β4 in human malignancies

Stewart

O’Connor

2015

Laboratory Investigation

182

181

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“…Adhesion receptors include cadherins, integrins, selectins, and the immunoglobulin superfamily (Dahlman et al 1998). Compared with normal thyroid and differentiated cancers, ATCs have reduced cadherin 1, type 1, E-cadherin (epithelial) (Dahlman et al 1998, Husmark et al 1999) and increased integrin α2β1 subunit expression (Dahlman et al 1998).…”

Section: Functional Genomicsmentioning

confidence: 99%

“…Compared with normal thyroid and differentiated cancers, ATCs have reduced cadherin 1, type 1, E-cadherin (epithelial) (Dahlman et al 1998, Husmark et al 1999) and increased integrin α2β1 subunit expression (Dahlman et al 1998). Normal cells at high density become growth arrested at the G1 phase.…”

Section: Functional Genomicsmentioning

confidence: 99%

Anaplastic thyroid cancer: molecular pathogenesis and emerging therapies

Smallridge¹,

Marlow²,

Copland³

2009

Endocrine-Related Cancer

362

275

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Anaplastic thyroid cancer (ATC) is a rare malignancy. While external beam radiation therapy has improved locoregional control, the median survival of w 4 months has not changed in more than half a century due to uncontrolled systemic metastases. The objective of this study was to review the literature in order to identify potential new strategies for treating this highly lethal cancer. PubMed searches were the principal source of articles reviewed. The molecular pathogenesis of ATC includes mutations in BRAF, RAS, catenin (cadherin-associated protein), beta 1, PIK3CA, TP53, AXIN1, PTEN, and APC genes, and chromosomal abnormalities are common. Several microarray studies have identified genes and pathways preferentially affected, and dysregulated microRNA profiles differ from differentiated thyroid cancers. Numerous proteins involving transcription factors, signaling pathways, mitosis, proliferation, cell cycle, apoptosis, adhesion, migration, epigenetics, and protein degradation are affected. A variety of agents have been successful in controlling ATC cell growth both in vitro and in nude mice xenografts. While many of these new compounds are in cancer clinical trials, there are few studies being conducted in ATC. With the recent increased knowledge of the many critical genes and proteins affected in ATC, and the extensive array of targeted therapies being developed for cancer patients, there are new opportunities to design clinical trials based upon tumor molecular profiling and preclinical studies of potentially synergistic combinatorial novel therapies.

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“…The a 2 b 1 integrin heterodimer is classically a collagen and laminin receptor limited to the basal surface when expressed by epithelia, but is present at contact sites between keratinocytes, suggesting that this integrin can also serve as an intercellular adhesion molecule and/or ligand bridging receptor (Symington et al 1993). It is noteworthy that a 2 b 1 expression is enhanced in some proliferating and migrating epithelia, including carcinomas, showing a circumferential cell staining pattern nearly identical to E-cadherin (Zutter & Santoro 1990, Dahlman et al 1998. In the present study, there was a dramatic induction of a 2 b 1 along the entire basolateral surface of LE and GE in response to progesterone.…”

Section: Progesterone Effects On Development Of Pig Gementioning

confidence: 99%

Effects of long-term progesterone on developmental and functional aspects of porcine uterine epithelia and vasculature: progesterone alone does not support development of uterine glands comparable to that of pregnancy

Bailey¹,

Dunlap²,

Frank³

et al. 2010

Reproduction

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In pigs, endometrial functions are regulated primarily by progesterone and placental factors including estrogen. Progesterone levels are high throughout pregnancy to stimulate and maintain secretion of histotroph from uterine epithelia necessary for growth, implantation, placentation, and development of the conceptus (embryo and its extra-embryonic membranes). This study determined effects of longterm progesterone on development and histoarchitecture of endometrial luminal epithelium (LE), glandular epithelium (GE), and vasculature in pigs. Pigs were ovariectomized during diestrus (day 12), and then received daily injections of either corn oil or progesterone for 28 days. Prolonged progesterone treatment resulted in increased weight and length of the uterine horns, and thickness of the endometrium and myometrium. Hyperplasia and hypertrophy of GE were not evident, but LE cell height increased, suggesting elevated secretory activity. Although GE development was deficient, progesterone supported increased endometrial angiogenesis comparable to that of pregnancy. Progesterone also supported alterations to the apical and basolateral domains of LE and GE. Dolichos biflorus agglutinin lectin binding and a v integrin were downregulated at the apical surfaces of LE and GE. Claudin-4, a 2 b 1 integrin, and vimentin were increased at basolateral surfaces, whereas occludins-1 and -2, claudin-3, and E-cadherin were unaffected by progesterone treatment indicating structurally competent trans-epithelial adhesion and tight junctional complexes. Collectively, the results suggest that progesterone affects LE, GE, and vascular development and histoarchitecture, but in the absence of ovarian or placental factors, it does not support development of GE comparable to pregnancy. Furthermore, LE and vascular development are highly responsive to the effects of progesterone.

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Integrins in thyroid tissue: upregulation of alpha2beta1 in anaplastic thyroid carcinoma

Cited by 26 publications

References 53 publications

Clinical significance of the integrin α6β4 in human malignancies

Clinical significance of the integrin α6β4 in human malignancies

Anaplastic thyroid cancer: molecular pathogenesis and emerging therapies

Effects of long-term progesterone on developmental and functional aspects of porcine uterine epithelia and vasculature: progesterone alone does not support development of uterine glands comparable to that of pregnancy

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