Loss of annexin A1 expression in human breast cancer detected by multiple high-throughput analyses

Shen, Dejun; Chang, Helena R.; Chen, Zugen; He, Jianbo; Lonsberry, Victor; Elshimali, Yahya; Chia, David; Seligson, David B.; Goodglick, Lee; Nelson, Stanley F.; Gornbein, Jeffrey

doi:10.1016/j.bbrc.2004.10.214

Cited by 71 publications

(62 citation statements)

References 35 publications

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“…Breast carcinomas that are positive for estrogen and progesterone receptors have been shown to be ANXA1 negative (Cao et al, 2008), confirming previous reports that ANXA1 expression is lost in human breast cancer epithelial cells (Shen et al, 2005;Ang et al, 2009). However, triple negative, or estrogen receptor, progesterone receptor and Her2/neu negative breast cancers were to be ANXA1 positive (Cao et al, 2008).…”

Section: Discussionsupporting

confidence: 83%

Annexin-1 interacts with NEMO and RIP1 to constitutively activate IKK complex and NF-κB: implication in breast cancer metastasis

et al. 2011

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The molecular mechanisms underlying constitutive nuclear factor-jB (NF-jB) activation in solid tumors has not been elucidated. We show that Annexin-1 (ANXA1) is involved in this process, and suppression of ANXA1 in highly metastatic breast cancer cells impedes migration and metastasis capabilities in vitro and in vivo. ANXA1 expression correlates with NF-jB activity, suggesting that ANXA1 may be required for the constitutive activity of IjB kinase (IKK) and NF-jB in highly metatstatic breast cancer. Gel-filtration analysis demonstrated that ANXA1 co-elutes with the members of the IKK complex and NF-jB signaling pathway, and immunoprecipitation confirmed that ANXA1 can bind to and interact with IKKc or NEMO, but not IKKa or IKKb. Importantly, silencing of ANXA1 prevents the interaction of NEMO and RIP1, which indicates that ANXA1 is required for the recruitment of RIP1 to the IKK complex, which may be important for the activation of NF-jB. Downstream targets of NF-jB include uPA and CXCR4, which can be modulated by ANXA1 silencing. CXCR4-mediated migration of breast cancer cell lines in response to CXCL12 was significantly modulated by ANXA1, indicating its importance in the tissue-specific migration of breast cancer cells. Chromatin immunoprecipitation experiments confirmed that in ANXA1 overexpressed cells, NF-jB was recruited to CXCR4 promoter without external stimulation, indicating that ANXA1 is critical for the constitutive activation of NF-jB in breast cancer to promote metastasis. Finally, we show that ANXA1 overexpression enhances metastasis and reduces survival in an intracardiac metastasis model, while ANXA1-deficient mice crossed with MMTV-PyMT mice display significantly less metastasis than their heterozygous littermates, indicating that ANXA1 is an important gene in breast cancer metastasis. Our data reveal that ANXA1 can constitutively activate NF-jB in breast cancer cells through the interaction with the IKK complex, and suggests that modulating ANXA1 levels has therapeutic potential to suppress breast cancer metastasis.

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Section: Discussionsupporting

confidence: 83%

Annexin-1 interacts with NEMO and RIP1 to constitutively activate IKK complex and NF-κB: implication in breast cancer metastasis

et al. 2011

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“…Several other studies have shown that ANXA1 expression also changes during the development and progression of cancer. 17 It is down-regulated in head and neck, 8 prostate 12 and breast cancers. 17 The ANXA1 protein expression was decreased in these cancers compared with normal epithelium suggesting that this protein is an essential component for maintenance of the normal epithelial phenotype, a fact that may be important in early events in invasive cancer.…”

Section: Discussionmentioning

confidence: 99%

“…17 It is down-regulated in head and neck, 8 prostate 12 and breast cancers. 17 The ANXA1 protein expression was decreased in these cancers compared with normal epithelium suggesting that this protein is an essential component for maintenance of the normal epithelial phenotype, a fact that may be important in early events in invasive cancer. 10 Based on our findings demonstrating the down-regulation of ANXA1 expression in laryngeal tumor cells in vivo, we went on to investigate the effect of exogenous ANXA1 on Hep-2 larynx cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…Down-regulation of ANXA1 was reported in many types of cancers, including in head and neck, 8,10 esophageal, 10 gastric, 16 prostate 10,12 and breast. 17 The altered expression of annexins has also been associated with cell line transformation, tumor progression and metastasis, and interpreted to suggest either a homeostatic or possible tumor suppressive role for annexins. 8 ANXA1 also has been reported in inflammatory cells, particularly in mast cells involved in the inflammatory responses.…”

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confidence: 99%

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Annexin 1: Differential expression in tumor and mast cells in human larynx cancer

Silistino-Souza

Rodrigues-Lisoni

Cury

et al. 2007

Intl Journal of Cancer

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Annexin 1 protein (ANXA1) expression was evaluated in tumor and mast cells in human larynx cancer and control epithelium. The effect of the exogenous ANXA1 (peptide Ac 2-26) was also examined during the cellular growth of the Hep-2 human larynx epidermoid carcinoma cell line. This peptide inhibited the proliferation of the Hep-2 cells within 144 hr. In surgical tissue specimens from 20 patients with larynx cancer, ultrastructural immunocytochemistry analysis showed in vivo down-regulation of ANXA1 expression in the tumor and increased in mast cells and Hep-2 cells treated with peptide Ac2-26. Combined in vivo and in vitro analysis demonstrated that ANXA1 plays a regulatory role in laryngeal cancer cell growth. We believe that a better understanding of the regulatory mechanisms of ANXA1 in tumor and mast cells may lead to future biological targets for the therapeutic intervention of human larynx cancer. ' 2007 Wiley-Liss, Inc.

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“…ANXA1 is also relevant to regulation of cell growth and apoptosis. Reduced expression of ANXA1 has been observed in many different human malignancies, including esophageal cancer (4), prostate cancer (5), breast cancer (6), and B-cell lymphoma (7). In addition, overexpression of ANXA1 in malignant tumor cells resulted in growth suppression and/or apoptosis (8).…”

mentioning

confidence: 99%

Truncation of Annexin A1 Is a Regulatory Lever for Linking Epidermal Growth Factor Signaling with Cytosolic Phospholipase A2 in Normal and Malignant Squamous Epithelial Cells

Sakaguchi

Murata

Sonegawa

et al. 2007

Journal of Biological Chemistry

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Regulation of cell growth and apoptosis is one of the pleiotropic functions of annexin A1 (ANXA1). Although previous reports on the overexpression of ANXA1 in many human cancers and on growth suppression and/or induction of apoptosis by ANXA1 may indicate the tumor-suppressive nature of ANXA1, molecular mechanisms of the function of ANXA1 remain largely unknown. Here we provide evidence that ANXA1 mechanistically links the epidermal growth factor-triggered growth signal pathway with cytosolic phospholipase A 2 (cPLA 2 ), an initiator enzyme of the arachidonic acid cascade, through interaction with S100A11 in normal human keratinocytes (NHK). Ca 2؉ -dependent binding of S100A11 to ANXA1 facilitated the binding of the latter to cPLA 2 , resulting in inhibition of cPLA 2 activity, which is essential for the growth of NHK. On exposure of NHK to epidermal growth factor, ANXA1 was cleaved solely at Trp 12 , and this cleavage was executed by cathepsin D. In squamous cancer cells, this pathway was shown to be constitutively activated. The newly found mechanistic intersection may be a promising target for establishing new measures against human cancer and other cell growth disorders.

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Loss of annexin A1 expression in human breast cancer detected by multiple high-throughput analyses

Cited by 71 publications

References 35 publications

Annexin-1 interacts with NEMO and RIP1 to constitutively activate IKK complex and NF-κB: implication in breast cancer metastasis

Annexin-1 interacts with NEMO and RIP1 to constitutively activate IKK complex and NF-κB: implication in breast cancer metastasis

Annexin 1: Differential expression in tumor and mast cells in human larynx cancer

Truncation of Annexin A1 Is a Regulatory Lever for Linking Epidermal Growth Factor Signaling with Cytosolic Phospholipase A2 in Normal and Malignant Squamous Epithelial Cells

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