Focal adhesion proteins as markers of malignant transformation and prognostic indicators in breast carcinoma

Madan, Rashna; Smolkin, Matthew B.; Cocker, Rubina; Fayyad, Rana; Oktay, Maja H.

doi:10.1016/j.humpath.2005.09.024

Cited by 77 publications

(70 citation statements)

References 25 publications

(31 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our data combined with that of others (Ito et al, 2002;Diaz et al, 2006;Madan et al, 2006;Planas-Silva et al, 2006), suggests that compared to normal breast epithelium, increased levels of activated c-Src are present in DCIS and invasive breast carcinoma. Activated c-Src levels correlated with HER2 expression, a higher tumour nuclear grade, the presence of comedo necrosis, and higher epithelial proliferative status.…”

Section: Discussionsupporting

confidence: 82%

Activated c-SRC in ductal carcinoma in situ correlates with high tumour grade, high proliferation and HER2 positivity

et al. 2006

View full text Add to dashboard Cite

Overexpression and/or activity of c-Src non-receptor tyrosine kinase is associated with progression of several human epithelial cancers including breast cancer. c-Src activity in 'pure' ductal carcinoma in situ (DCIS) was measured to assess whether this predicts recurrence and/or correlates with HER2 expression and other clinical parameters. Activated c-Src levels were evaluated in DCIS biopsies from 129 women, with median follow-up at 60 months. High levels of activated c-Src correlated with HER2 positivity, high tumour grade, comedo necrosis and elevated epithelial proliferation. In univariate analysis, high activated c-Src level associated with lower recurrence-free survival at 5 years (P ¼ 0.011). Thus, high c-Src activity may identify a subset of DCIS with high risk of recurrence or progression to invasive cancer where therapeutics targeting c-Src may benefit this patient subset.

show abstract

Section: Discussionsupporting

confidence: 82%

Activated c-SRC in ductal carcinoma in situ correlates with high tumour grade, high proliferation and HER2 positivity

et al. 2006

View full text Add to dashboard Cite

show abstract

“…The novel observation is that TGF-b receptors can also be incorporated into these domains. Cell attachment through integrins and subsequent signaling requires Src and FAK activity (Madan et al, 2006). In this study, we showed that Src activity is required for collageninduced Smad activation but not for the TGF-b1-generated signaling process.…”

Section: Discussionmentioning

confidence: 61%

Extracellular matrix-induced transforming growth factor-β receptor signaling dynamics

Garamszegi

Samavarchi-Tehrani

et al. 2010

Oncogene

View full text Add to dashboard Cite

Matrix remodeling, degradation, inflammation and invasion liberate peptide fragments that can subsequently interact with cells in an attachment-independent manner. Such 'soluble' matrix components, including collagens, fibronectin and laminin, induced Smad activation (termed crosstalk signaling), which follows a similar chronological sequence and R-Smad specificity as induced by transforming growth factor (TGF)-b1. Smad4 nuclear translocation occurred in response to collagen binding, indicating downstream signal propagation. TGF-b scavenging antibody affected only TGF-b1, but not crosstalk-induced responses. TGF-b type II receptor mutation (DR26D25), which is deficient in TGF-b type I receptor recruitment to the ligand, induced a heterotetramer signaling complex, and propagated Smad2 activation only through collagen induction and not TGF-b signaling. Consequentially, TGF-b ligand participation is not required for crosstalk signaling. This signaling requires a functional integrin b1 receptor as showed by RNA interference. Co-immunoprecipitation (co-IP) and fluorescent microscopy indicate the involvement of focal adhesion kinase (FAK) and Src activity in collagen-induced signal propagation, and suggest a membrane signaling complex formation that includes both TGF-b receptors and integrins. The related gene expressional responses are distinct from that evoked by TGF-b1, supporting its separate function. This signaling mechanism expands and partially explains TGFb receptor dynamics and consequential signaling diversityrelated gene expressional plasticity.

show abstract

“…12 We were able to describe paxillin expression with a wider range of functional alterations, and half of the benign cases were positive. In contrast to another report, 12 we did not find any association between paxillin expression and progression to malignancy or BI-RADS classification. However, when assessed in cytological smears, paxillin failed to reach any concordance with invasion or prognostic variables.…”

Section: Fra-1 Expression Was Always Evident Around Ductal Structuresmentioning

confidence: 87%

“…12 Paxillin is an adaptor protein with an important role in cell spreading and motility, 13 and is located in the region of cell contact with the underlying extracellular matrix. In the physiological state, it functions as an adaptor protein that recruits several cytoskeleton and signaling proteins into a complex, thereby enabling transmission of coordinated downstream signals.…”

Section: Introductionmentioning

confidence: 99%

Expression of claudin, paxillin and FRA-1 in non-nodular breast lesions in association with microcalcifications

et al. 2013

View full text Add to dashboard Cite

CONTEXT AND OBJECTIVE: The possible role of adhesion molecules in early breast carcinogenesis has been shown in the literature. We aimed to analyze early adhesion imbalances in non-nodular breast lesions and their association with precursor lesions, in order to ascertain whether these alterations exist and contribute towards early carcinogenesis. DESIGN AND SETTING: Retrospective cross-sectional study based on medical records at a private radiological clinic in São Paulo, Brazil. METHODS:We retrospectively reviewed the medical records of all consecutive women attended between August 2006 and July 2007 who presented mammographic evidence of breast microcalcifications classified as Breast Imaging Reporting and Data System Atlas (BI-RADS) type 4. These women underwent stereotaxic biopsy. Clinical, radiological and pathological data were collected, and immunohistochemical assays searched for claudin, paxillin, FRA-1 and HER-2. RESULTS: Over this period, 127 patients were evaluated. Previous BI-RADS diagnoses showed that 69 cases were in category 4A, 47 in 4B and 11 in 4C. Morphological assessment showed benign entities in 86.5%. Most of the benign lesions showed preserved claudin expression, associated with paxillin (P < 0.001). Paxillin and HER-2 expressions were correlated. FRA-1 expression was also strongly associated with HER-2 expression (P < 0.001). CONCLUSIONS: Although already present in smaller amounts, imbalance of adhesion molecules is not necessarily prevalent in non-nodular breast lesions. Since FRA-1 expression reached statistically significant correlations with radiological and morphological diagnoses and HER-2 status, it may have a predictive role in this setting. RESUMO CONTEXTO E OBJETIVO:A literatura tem mostrado a importância de moléculas de adesão na carcinogê-nese precoce de mama. Objetivamos analisar desequilíbrios precoces de adesão em lesões não nodulares da mama e associação com lesões precursoras, a fim de verificar se essas alterações existem e contribuem com a carcinogênese. . A maioria das lesões benignas mostrou expressão preservada de claudina, associada a paxilina (P < 0,001). Expressões de paxilina e HER-2 foram correlacionadas. Expressão de FRA-1 associou-se à de HER-2 (P < 0,001). CONCLUSÕES: Embora já presente em menor quantidade, o desequilíbrio de moléculas de adesão não é necessariamente prevalente em lesões mamárias nodulares e talvez a expressão de FRA-1 possa ter um papel preditivo neste cenário, uma vez que atingiu correlações estatisticamente significativas com o diagnóstico radiológico e morfológico e com o status de HER-2.

show abstract

Focal adhesion proteins as markers of malignant transformation and prognostic indicators in breast carcinoma

Cited by 77 publications

References 25 publications

Activated c-SRC in ductal carcinoma in situ correlates with high tumour grade, high proliferation and HER2 positivity

Activated c-SRC in ductal carcinoma in situ correlates with high tumour grade, high proliferation and HER2 positivity

Extracellular matrix-induced transforming growth factor-β receptor signaling dynamics

Expression of claudin, paxillin and FRA-1 in non-nodular breast lesions in association with microcalcifications

Contact Info

Product

Resources

About