The expression and modulation of CEACAM1 and tumor cell transformation

Fiori, Valentina; Magnani, Mauro; Cianfriglia, Maurizio

doi:10.4415/ann_12_02_09

Cited by 36 publications

(17 citation statements)

References 67 publications

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“…In addition to its positive effect on eNOS expression, CEACAM1 promotes membrane (caveolar) targeting of eNOS by acting as a membrane anchor and by preserving eNOS palmitoylation, thus supporting proper eNOS activity (1). CEACAM1 limits proatherosclerotic LEI by suppression of adhesion molecule expression and by repression of glycocalyx-degrading enzymes, thus preserving the integrity of the endothelial glycocalyx (2). CEACAM1 is involved in the initial steps of AJ establishment by interaction with b-catenin/VEcadherin complex and differentially regulates their stability (3).…”

Section: Discussionmentioning

confidence: 99%

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Endothelial barrier function is differentially regulated by CEACAM1‐mediated signaling

Ghavampour¹,

Kleefeldt²,

Bömmel³

et al. 2018

FASEB j.

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Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) is known to be crucial to vasculogenesis and angiogenesis. Recently, CEACAM1 deficiency was shown to result in the formation of aortic plaque-like lesions, indicating a role for CEACAM1 in adult vessels as well. The underlying mechanisms remained largely elusive. Therefore, we aimed to elucidate the role of CEACAM1 in endothelial homeostasis. Here, we show that CEACAM1 deficiency causes subcellular eNOS redistribution in endothelial cells ( i.e., by eNOS depalmitoylation) and alters endothelial glycocalyx that confers antiadhesive properties to the endothelium ( i.e., by repression of glycocalyx-degrading enzymes). Accordingly, our analysis revealed an increased leukocyte-endothelial interaction in CEACAM1-deficient endothelium. In addition, CEACAM1 age dependently modulated basal and TNF-α-mediated endothelial barrier (EB) leakiness. In younger mice, CEACAM1 was protective for EB, whereas in aged mice it promoted EB leakiness. EB function depends on interendothelial adherence junctions formed by β-catenin/vascular endothelial-cadherin complexes. We show here that CEACAM1 influenced basal and TNF-α-mediated phosphorylation of β-catenin and caveolin-1, which are essential players in EB modulation. Both increased adhesiveness to leukocytes and EB modulation due to CEACAM1 deficiency may facilitate inflammatory cell transmigration into the vascular wall and subsequent plaque formation. Collectively, these results identify a crucial role for CEACAM1 in endothelial homeostasis of adult blood vessels.-Ghavampour, S., Kleefeldt, F., Bömmel, H., Volland, J., Paus, A., Horst, A., Pfeiffer, V., Hübner, S., Wagner, N., Rueckschloss, U., Ergün, S. Endothelial barrier function is differentially regulated by CEACAM1-mediated signaling.

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Section: Discussionmentioning

confidence: 99%

“…Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) is a member of the Ig superfamily implicated in pathogen recognition, immunomodulation, tumor growth, and metastasis (2,3). Although CEACAM1 is an important mediator of vascularization and angiogenesis (4)(5)(6), its role in the homeostasis of adult blood vessels is largely unknown.…”

mentioning

confidence: 99%

Endothelial barrier function is differentially regulated by CEACAM1‐mediated signaling

Ghavampour¹,

Kleefeldt²,

Bömmel³

et al. 2018

FASEB j.

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“…In recent years, an increasing number of studies have shown that aberrant expression of CEACAM1 contributes to the initiation and progression of cancers [24]. Moreover, the physiological and pathological roles of CEACAM1 have been demonstrated in most malignant tumor types, and CEACAM1 seems to be of great importance in the diagnosis and treatment of cancers [4].…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of CEACAM1 in breast cancer

Yang

Liu

et al. 2015

ABBS

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Carcinoembryonic antigen-related adhesion molecule 1 (CEACAM1) is a type 1 transmembrane glycoprotein belonging to the CEA family, which has been found to exist as either soluble forms in body fluids or membrane-bound forms on the cell surface. Aberrant CEACAM1 expression is associated with tumor progression and has been found in a variety of human malignancies. Increasing interest has been devoted to the expression of CEACAM1 in breast cancer, but most of these findings are contradictory. The aim of this study was to investigate CEACAM1 expression in breast cancer in greater detail. Using immunohistochemical staining, we found that CEACAM1 expression was reduced or lost in breast cancer tissues compared with noncancerous breast tissues. In addition, soluble CEACAM1 levels in the culture medium of breast cancer cell lines were significantly lower than those in a nontumorigenic breast epithelial cell line. Immunofluorescence analysis consistently showed that breast cancer cell lines have relatively low expression of membrane-bound CEACAM1. Furthermore, CEACAM1 mRNA and protein expression levels were down-regulated in breast cancer cell lines as measured using real-time reverse transcriptase-polymerase chain reaction and western blot analysis, respectively. Taken together, our results demonstrate a systematic down-regulation of CEACAM1 in breast cancer and suggest that a strategy to restore CEACAM1 expression may be helpful for the treatment of breast cancer.

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“…CEACAM1 is expressed as a co-receptor on a variety of immune and parenchymal cell types as well on neoplastic and developing tissues with important functional implications. There are a number of excellent reviews on these topics [87][88][89][90]. Here we will focus on the role played by CEACAM1 in the immune system where it functions in both innate and adaptive immunity.…”

Section: Ceacam1 Modulates the Immune Responsementioning

confidence: 99%

CEACAM1 structure and function in immunity and its therapeutic implications

Kim

Huang

Gandhi

et al. 2019

Seminars in Immunology

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The type I membrane protein receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) distinctively exhibits significant alternative splicing that allows for tunable functions upon homophilic binding. CEACAM1 is highly expressed in the tumor environment and is strictly regulated on lymphocytes such that its expression is restricted to activated cells where it is now recognized to function in tolerance pathways. CEACAM1 is also an important target for microbes which have co-opted these attributes of CEACAM1 for the purposes of invading the host and evading the immune system. These properties, among others, have focused attention on CEACAM1 as a unique target for immunotherapy in autoimmunity and cancer. This review examines recent structural information derived from the characterization of CEACAM1:CEACAM1 interactions and heterophilic modes of binding especially to microbes and how this relates to CEACAM1 function. Through this, we aim to provide insights into targeting CEACAM1 for therapeutic intervention.

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The expression and modulation of CEACAM1 and tumor cell transformation

Cited by 36 publications

References 67 publications

Endothelial barrier function is differentially regulated by CEACAM1‐mediated signaling

Endothelial barrier function is differentially regulated by CEACAM1‐mediated signaling

Down-regulation of CEACAM1 in breast cancer

CEACAM1 structure and function in immunity and its therapeutic implications

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