Down-regulation of CEACAM1 in breast cancer

Yang, Changcheng; He, Ping; Liu, Yiwen; He, Yiqing; Yang, Cuixia; Du, Yan; Zhou, Min; Wang, Wenjuan; Zhang, Guoliang; Wu, Man; Gao, Feng

doi:10.1093/abbs/gmv075

Cited by 25 publications

(20 citation statements)

References 24 publications

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“…Cytochrome c ‐mediated apoptosis of a cell involves many complex biochemical steps . Of the different biomolecules involved, caspase‐3 plays the most crucial role in apoptosome formation once cyt c is released from the mitochondria.…”

Section: Resultsmentioning

confidence: 99%

Cytochrome c‐Capped Fluorescent Gold Nanoclusters: Imaging of Live Cells and Delivery of Cytochrome c

Amin

Bhattacharyya

2016

ChemPhysChem

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Cytochrome c-capped fluorescent gold nanoclusters (Au-NCs) are used for imaging of live lung and breast cells. Delivery of cytochrome c inside the cells is confirmed by covalently attaching a fluorophore (Alexa Fluor 594) to cytochrome c-capped Au-NCs and observing fluorescence from Alexa 594 inside the cell. Mass spectrometry studies suggest that in bulk water, addition of glutathione (GSH) to cytochrome c-capped Au-NCs results in the formation of glutathione-capped Au-NCs and free apo-cytochrome c. Thus glutathione displaces cytochrome c as a capping agent. Using confocal microscopy, the emission spectra and decay of Au-NCs are measured in live cells. From the position of the emission maximum it is shown that the Au-NCs exist as Au8 in bulk water and as Au13 inside the cells. Fluorescence resonance energy transfer from cytochrome c-Au-NC (donor) to Mitotracker Orange (acceptor) indicates that the Au-NCs localise in the mitochondria of live cells.

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Section: Resultsmentioning

confidence: 99%

Cytochrome c‐Capped Fluorescent Gold Nanoclusters: Imaging of Live Cells and Delivery of Cytochrome c

Amin

Bhattacharyya

2016

ChemPhysChem

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“…Although CEACAM1 down-regulation is an early event in tumorigenesis for a number of cancers including breast cancer (22)(23)(24), the mechanism of down-regulation and subsequent effects are unclear. However, the observation that CEACAM1 expression is luminal in most normal tissues and correlates with lumen formation in a three-dimensional model of lumenogenesis, suggests its expression is coordinated with lumen formation, a phenotype lost in hyperplasia, ductal carcinoma in situ, and invasive tumors (25).…”

Section: Discussionmentioning

confidence: 99%

Induction of Lumen Formation in a Three-dimensional Model of Mammary Morphogenesis by Transcriptional Regulator ID4

Shively

2016

Journal of Biological Chemistry

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Concomitant loss of lumen formation and cell adhesion protein CEACAM1 is a hallmark feature of breast cancer. In a threedimensional culture model, transfection of CEACAM1 into MCF7 breast cells can restore lumen formation by an unknown mechanism. ID4, a transcriptional regulator lacking a DNA binding domain, is highly up-regulated in CEACAM1-transfected MCF7 cells, and when down-regulated with RNAi, abrogates lumen formation. Conversely, when MCF7 cells, which fail to form lumena in a three-dimensional culture, are transfected with ID4, lumen formation is restored, demonstrating that ID4 may substitute for CEACAM1. After showing the ID4 promoter is hypermethylated in MCF7 cells but hypomethylated in MCF/ CEACAM1 cells, ID4 expression was induced in MCF7 cells by agents affecting chromatin remodeling and methylation. Mechanistically, CaMK2D was up-regulated in CEACAM1-transfected cells, effecting phosphorylation of HDAC4 and its sequestration in the cytoplasm by the adaptor protein 14-3-3. CaMK2D also phosphorylates CEACAM1 on its cytoplasmic domain and mutation of these phosphorylation sites abrogates lumen formation. Thus, CEACAM1 is able to maintain the active transcription of ID4 by an epigenetic mechanism involving HDAC4 and CaMK2D, and the same kinase enables lumen formation by CEACAM1. Because ID4 can replace CEACAM1 in parental MCF7 cells, it must act downstream from CEACAM1 by inhibiting the activity of other transcription factors that would otherwise prevent lumen formation. This overall mechanism may be operative in other cancers, such as colon and prostate, where the down-regulation of CEACAM1 is observed.Lumen formation, a central feature of mammary morphogenesis, is lost during mammary tumorigenesis, starting with filling in the lumen with cancer cells in ductal carcinoma in situ (1) and becoming more evident in invasive solid tumors (2). Identification of the molecules that change during this process and the underlying mechanisms causing these changes are major goals of breast cancer research. Among the many molecules identified so far, CEACAM1 stands out as a luminal expressed protein that is rapidly down-regulated in both ductal carcinoma in situ (3) and invasive breast cancer (2). Not surprisingly, luminal expression of CEACAM1 occurs throughout ductal tissues such as the liver, digestive and urogenital tract, and prostate, and its loss upon malignant transformation is one of the earliest events observed (4). To study its role in lumen formation, we originally placed MCF10F, a cell line that expresses CEACAM1, in a three-dimensional culture system pioneered by Bissell and co-workers (5), and observed lumen formation with CEACAM1 at the luminal surface (3). When its expression was blocked by antisense, anti-CEACAM1 antibody, or peptides derived from the N terminus of CEACAM1, lumen formation was abrogated, demonstrating that its expression played a central role in the complex process of lumenogenesis (3). As a next step, we demonstrated that MCF7 breast cancer cells that fail to express CEACAM1 o...

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“…Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) is a transmembrane glycoprotein involved in cell-cell adhesion, and its abnormal expression is associated with a variety of human malignancies [46,47]. CEACAM1 alternative splicing generates 12 isoforms, resulting in three C2-like domains and forming isoforms that differ in the length of the extracellular region [48].…”

Section: Ceacam1mentioning

confidence: 99%

Influence of transcriptional variants on metastasis

Poloni

Bonatto

2018

RNA Biology

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Cancer metastasis is defined as the dissemination of malignant cells from the primary tumor site, leading to colonization of distant organs and the establishment of a secondary tumor. Metastasis is frequently associated with chemoresistance and is the major cause of cancer-related mortality. Metastatic cells need to acquire the ability to resist to stresses provided by different environments, such as reactive oxygen species, shear stress, hemodynamic forces, stromal composition, and immune responses, to colonize other tissues. Hence, only a small population of cells has a metastasis-initiating potential. Several studies have revealed the misregulation of transcriptional variants during cancer progression, and many splice events can be used to distinguish between normal and tumoral tissue. These variants, which are abnormally expressed in malignant cells, contribute to an adaptive response of tumor cells and the success of the metastatic cascade, promoting an anomalous cell cycle, cellular adhesion, resistance to death, cell survival, migration and invasion. Understanding the different aspects of splicing regulation and the influence of transcriptional variants that control metastatic cells is critical for the development of therapeutic strategies. In this review, we describe how transcriptional variants contribute to metastatic competence and discuss how targeting specific isoforms may be a promising therapeutic strategy.

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Down-regulation of CEACAM1 in breast cancer

Cited by 25 publications

References 24 publications

Cytochrome c‐Capped Fluorescent Gold Nanoclusters: Imaging of Live Cells and Delivery of Cytochrome c

Cytochrome c‐Capped Fluorescent Gold Nanoclusters: Imaging of Live Cells and Delivery of Cytochrome c

Induction of Lumen Formation in a Three-dimensional Model of Mammary Morphogenesis by Transcriptional Regulator ID4

Influence of transcriptional variants on metastasis

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