Role of Fos‐related antigen 1 in the progression and prognosis of ductal breast carcinoma

Logullo, Ângela Flávia; Stiepcich, Monica Maria; Osório, Cynthia Aparecida Bueno de Toledo; Nonogaki, Sueli; Pasini, Fátima Solange; Rocha, Rafael Malagoli; Soares, Fernando Augusto; Brentani, Maria Mitzi

doi:10.1111/j.1365-2559.2011.03785.x

Cited by 20 publications

(22 citation statements)

References 35 publications

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“…Fra-1 frequently is overexpressed in human solid tumors as well as in many cell lines derived from such tumors (20,21,(25)(26)(27)(28). To investigate whether Fra-1 has a more general role in metastasis, we focused on human breast cancer, in which several lines of evidence suggest a role for Fra-1 in metastatic disease.…”

Section: Suppression Of Fra-1 Abrogates the Metastatic Potential Of Hmentioning

confidence: 99%

“…Indeed, Fra-1 commonly is overexpressed in human breast cancer and derived cell lines, including the triple [ER/ progesterone receptor/ human epidermal growth factor receptor 2 (Her2)]-negative and metastatic cell line MDA-MB-231 (SI Appendix, Fig. S6A), and its expression has been shown to correlate with, and regulate, the cell lines' invasive potential in vitro (19,21,25,27).…”

Section: Suppression Of Fra-1 Abrogates the Metastatic Potential Of Hmentioning

confidence: 99%

“…We next aimed to determine whether Fra-1 activity has prognostic value in estimating breast cancer recurrence. Immunohistochemical assessment of Fra-1 expression, although consistently reporting higher Fra-1 expression in neoplastic lesions, has delivered ambiguous results regarding its prognostic value (25)(26)(27). This ambiguity might result either from the technical limitations of current detection techniques or from the extensive regulation of Fra-1 by posttranslational modifications, so that its expression may not strictly correlate with its activity.…”

Section: Fra1-associated Gene-expression Profile Accurately Predicts mentioning

confidence: 99%

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Identification of a pharmacologically tractable Fra-1/ADORA2B axis promoting breast cancer metastasis

Desmet

Gallenne

Prieur

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

157

149

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Metastasis confronts clinicians with two major challenges: estimating the patient's risk of metastasis and identifying therapeutic targets. Because they are key signal integrators connecting cellular processes to clinical outcome, we aimed to identify transcriptional nodes regulating cancer cell metastasis. Using rodent xenograft models that we previously developed, we identified the transcription factor Fos-related antigen-1 (Fra-1) as a key coordinator of metastasis. Because Fra-1 often is overexpressed in human metastatic breast cancers and has been shown to control their invasive potential in vitro, we aimed to assess the implication and prognostic significance of the Fra-1-dependent genetic program in breast cancer metastasis and to identify potential Fra-1-dependent therapeutic targets. In several in vivo assays in mice, we demonstrate that stable RNAi depletion of Fra-1 from human breast cancer cells strongly suppresses their ability to metastasize. These results support a clinically important role for Fra-1 and the genetic program it controls. We show that a Fra-1-dependent gene-expression signature accurately predicts recurrence of breast cancer. Furthermore, a synthetic lethal drug screen revealed that antagonists of the adenosine receptor A 2B (ADORA2B) are preferentially toxic to breast tumor cells expressing Fra-1. Both RNAi silencing and pharmacologic blockade of ADORA2B inhibited filopodia formation and invasive activity of breast cancer cells and correspondingly reduced tumor outgrowth in the lungs. These data show that Fra-1 activity is causally involved in and is a prognostic indicator of breast cancer metastasis. They suggest that Fra-1 activity predicts responsiveness to inhibition of pharmacologically tractable targets, such as ADORA2B, which may be used for clinical interference of metastatic breast cancer.epithelial-mesenchymal transition | invasion T he path toward improved management of metastatic tumors, the major cause of death among cancer patients, involves tackling of two major challenges: the development of therapies that combat the patient's metastatic disease and of means of reliably assessing the individual patient's risk of developing metastasis. In line with the second objective, patient stratification has received increasing attention as a way to improve the therapeutic management of cancer patients. In recent years, for example, gene-expression profiling of primary breast cancer has uncovered gene signatures that assist clinicians in classifying breast cancer subtypes more accurately (1, 2) and that provide predictions of tumor recurrence and clinical outcome (3-5). Such classifiers have proven useful for formulating prognosis and adjusting therapeutic management of breast cancer patients, complementing conventional histopathological criteria such as tumor size, nodal status, and estrogen receptor (ER) status (6-8) to predict clinical outcome better.The most important challenge posed by metastatic cancer, blocking metastatic spread, has proven more troublesome. Indeed, most ...

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Section: Suppression Of Fra-1 Abrogates the Metastatic Potential Of Hmentioning

confidence: 99%

Section: Suppression Of Fra-1 Abrogates the Metastatic Potential Of Hmentioning

confidence: 99%

Section: Fra1-associated Gene-expression Profile Accurately Predicts mentioning

confidence: 99%

See 1 more Smart Citation

Identification of a pharmacologically tractable Fra-1/ADORA2B axis promoting breast cancer metastasis

Desmet

Gallenne

Prieur

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

157

149

View full text Add to dashboard Cite

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“…19 Interestingly, there are several reports in the literature regarding interactions between HER-2 expression (one of the most important receptor kinase growth factors in breast cancer) and adhesion molecules.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2013

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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.

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“…Regardless, one study proposes that the high accumulation of Fra-1 is induced by the PKCθ pathway and is critical to mediate the effect of this kinase on cell migration [244]. Moreover, Fra-1 has also been suspected in being involved with early events in carcinogenesis, as well as high grade tumors [245]. With that being said, most of these studies state that Fra-1 does not correlate to patient outcome and prognosis [242] [245] [246].…”

Section: Kumar Et Al Advances In Breast Cancer Researchmentioning

confidence: 99%

Role of ESR Pathway Genes in Breast Cancer: A Review

Kumar¹,

Myers²,

Homsi³

et al. 2018

ABCR

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Breast cancer is the leading cause of death in women. Prognosis of breast cancer is often pessimistic because the tumors are prone to metastasizing to the bone, brain, and lung. The estrogen signaling receptor (ESR) pathway contains 39 main genes and proteins which makes it one of the larger signaling pathways. Predominately this pathway and the proteins within are involved in breast growth and development, making it a prospective area of study for breast cancer. While the healthy ESR pathway has been constructed and is well established, a mechanistic model of mutated genes of ESR pathway has not been delved upon. Such mutated models could be utilized for selecting combinational targets for drug therapies, as well as elucidating crosstalk between other pathways and feedback mechanisms. To construct the mutated models of the ESR pathway it is imperative to assess what is currently understood in the literature and what inconsistencies exist in order to resolve them. Without this information, a model of the ESR pathway will be unreliable and likely unproductive. This review is the detailed literature survey of the biological studies performed on ESR pathways genes, and their respective roles in breast cancer. Furthermore, the details mentioned in the review can be beneficial for the integrated study of the ESR pathway genes, which includes, structural and dynamics study of the genes products, to have a holistic understanding of the cancer mechanism.

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Role of Fos‐related antigen 1 in the progression and prognosis of ductal breast carcinoma

Cited by 20 publications

References 35 publications

Identification of a pharmacologically tractable Fra-1/ADORA2B axis promoting breast cancer metastasis

Identification of a pharmacologically tractable Fra-1/ADORA2B axis promoting breast cancer metastasis

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

Role of ESR Pathway Genes in Breast Cancer: A Review

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