cDCC (Chicken homologue to a gene deleted in colorectal carcinoma) is an epithelial adhesion molecule expressed in the basal cells and involved in epithelial-mesenchymal interaction

doi:10.1006/dbio.1994.1208

Developmental Biology

Volume 164, Issue 2, August 1994, Pages 383-397

https://doi.org/10.1006/dbio.1994.1208 Get rights and content

Cloning of human DCC (deleted in colorectal carcinoma, Fearon et al., 1990) showed that it is an immunoglobulin superfamily member homologous to neural cell adhesion molecules (N-CAM). To explore the normal function of this molecule, we have cloned a chicken homologue to DCC (cDCC) and raised an antibody to DCC. cDCC is a protein of 160 kDa with an expression pattern distinct from those of other immunoglobulin family members including N-CAM and Ng-CAM. Transgene expression of cDCC in fibroblasts led to increased cell-cell adhesion. Localization studies in chicken and mouse embryos showed that DCC is expressed in the epithelia of skin, gut, lung, and bladder. In adult, the expression of DCC is limited to the basal layer of stratified epithelium in skin, crypt regions of intestinal villi, and stem cells in mammary duct. Cell aggregation assay using embryonic chicken skin epithelial cells and antibody to DCC showed it is a Ca²⁺ independent cell adhesion molecule. In epithelial-mesenchymal interactions during feather morphogenesis, antibody to DCC suppressed the formation of dermal condensations and the polarized localization of N-CAM and fibronectin. These results implied that DCC is an epithelial cell adhesion molecule required for mediating critical functions in epithelial-epithelial and epithelial-mesenchymal interactions.

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Cited by (50)

DCC regulates cell adhesion in human colon cancer derived HT-29 cells and associates with ezrin
2006, European Journal of Cell Biology
The deleted in colorectal cancer (DCC) gene encodes a 170- to 190-kDa protein of the Immunoglobulin superfamily. Firstly identified as a tumor suppressor gene in human colorectal carcinomas, the main function for DCC has been described in the nervous system as part of a receptor complex for netrin-1. Moreover, roles in mucosecretory cell differentiation and as inducer of apoptosis have also been reported. DCC knockout mice supported a crucial role for this gene in axonal migration, yet questioned its implication in tumor suppression and mucosecretory differentiation. The work presented here demonstrates that a DCC-transfected HT-29 colonic human cell line (HT-29/DCC) displays an increase in cell–cell adhesion to the detriment of cell–matrix interactions: HT-29/DCC cells exhibit more and better-structured desmosomes while focal adhesions and hemidesmosomes are disrupted. HT-29/DCC cells show no changes in adherent junctions but upon treatment with TPA, HT-29/DCC cells show resistance to scattering, and maintain E-cadherin in the membrane. In addition, the actin cytoskeleton is affected in HT-29/DCC cells: stress fibers are disrupted while cortical actin remains intact. We identified a putative ERM-M (ezrin/radixin/moesin and merlin) binding domain in the juxtamembrane region of the DCC protein. In vitro pull-down assays demonstrate the interaction of the DCC cytoplasmic domain with the N-terminal region of ezrin and merlin, and co-immunoprecipitation assays in transiently DCC-transfected COS-1 cells showed that the interaction between DCC and ezrin also takes place in vivo. Altogether, our results suggest that DCC could regulate cell adhesion and migration through its association with ERM-M proteins.
The Netrin family of guidance factors: Emphasis on Netrin-1 signalling
2005, Brain Research Reviews
During the development of the nervous system, neurons respond to the coordinated action of a variety of attractive and repulsive signals from the embryonic environment. Netrins form a family of extracellular proteins that regulate the migration of neurons and axonal growth cones. These proteins are bifunctional signals that are chemoattractive for some neurons and chemorepellent for others. Netrins mainly interact with the specific receptors DCC and UNC-5 family. To date, several Netrins have been described in mouse and humans: Netrin-1, -3/NTL2, -4/β and G-Netrins.
Netrin-1 is the most studied member of the family. It is involved in the development many projections of the nervous system. When Netrin-1 interacts with its specific receptors, a cascade of local cytoplasmic events is triggered. Several signal transduction pathways and effector molecules have been implicated in the response to Netrin-1: small Rho-GTPases, MAP-Kinases, second messengers and the Microtubule Associated Protein 1B (MAP1B).
Expression of p53, DCC, and HER-2/neu in mucinous carcinoma of the breast
2005, Kaohsiung Journal of Medical Sciences
We investigated the clinicopathologic and oncoprotein expression characteristics of 11 pure mucinous and 76 non-mucinous infiltrating ductal carcinomas in the human female breast. We compared patient age, tumor size, axillary lymph node status, and the expression of estrogen receptor (ER), progesterone receptor (PR), deleted-in-colon cancer (DCC), HER-2/neu, and p53. Mucinous carcinoma with axillary lymph node metastasis occurs less frequently than non-mucinous carcinoma (0% vs 63.1%; p = 0.0018). Compared with the non-mucinous type, mucinous carcinoma specimens have more DCC expression (100% vs 48.7%; p = 0.0027) and more ER expression (90.9% vs 26.9%; p = 0.0023), but less HER-2/neu overexpression (0% vs 38.1%; p = 0.0302). We confirmed that mucinous carcinoma samples from the breast reveal distinct clinicopathologic and oncoprotein expression features compared with non-mucinous carcinoma and, therefore, it seems reasonable to suggest different biologic characteristics and manifestations.
Expression of netrin-1 and netrin-1 receptor, DCC, in the rat olfactory nerve pathway during development and axonal regeneration
2002, Neuroscience
Netrin-1 is a bifunctional secreted protein that directs axon extension in various groups of developing axonal tracts. The transmembrane DCC (deleted in colorectal cancer) receptor is described as netrin-1 receptor and is involved in the attractive effects of netrin-1. In this study, we examined the spatio-temporal expression patterns of both netrin-1 and DCC in the rat olfactory system at different stages of development and during axonal regeneration following unilateral bulbectomy. High DCC expression was detected on the pioneer olfactory axons as they are extending toward the telencephalon. This expression was transient since from embryonic day 16 onwards, DCC was no longer detected along the olfactory nerve path. From embryonic day 14 until birth, DCC was also expressed within the mesenchyme surrounding the olfactory epithelium. During the same period, netrin-1 protein was detected along the trajectory of olfactory axons up to the olfactory bulb and its expression pattern in the nasal mesenchyme largely overlapped that of DCC. Moreover, netrin-1 continued to be present during the two first post-natal weeks, and a weak protein expression still persisted in the dorso-medial region of the olfactory epithelium in adult rats. While unilateral bulbectomy induced a transient up-regulation of netrin-1 in the lamina propria, particularly in the dorso-medial region of the neuroepithelium, no DCC expression was detected on the regenerating olfactory axons. In the developing olfactory bulb, the extension of mitral cell axons was associated with DCC presence while netrin-1 was absent along this axonal path. DCC was also highly expressed in the newly formed glomeruli after birth, and a weak DCC expression was still detected in the glomerular layer in adult rats.
Taken together, these data support the notion that netrin-1, via DCC expressed on axons, may play a role in promoting outgrowth and/or guidance of pioneering olfactory axons toward the olfactory bulb primordium. Moreover, association of netrin-1 with mesenchymal DCC may provide a permissive environment to the growth of both pioneer and later-growing axons. The maintenance of netrin-1 expression in the nasal mesenchyme of adult rats as well as its regional up-regulation following unilateral bulbectomy infer that netrin-1, even in the absence of DCC, may be involved in the process of axonal growth of newly differentiated olfactory receptor neurons probably through the use of other receptors.
Where the rubber meets the road: Netrin expression and function in developing and adult nervous systems
2002, Progress in Brain Research
Netrins are a family of secreted proteins that direct the migration of cells and axonal growth cones during neural development. They are bifunctional cues, attracting some cell types and repelling others. Netrins function as either short- or long-range cues, in some circumstances acting close to the surface of the cells that produce them and in other cases at a distance. Two classes of receptors mediate the response to netrin-1, the deleted in colorectal cancer family and the UNC-5 homolog family. Although netrin function has been extensively studied in the embryonic nervous system, netrin-1 is expressed in the adult mammalian spinal cord at a level similar to that in the embryonic CNS. In the adult and embryonic CNS, the majority of netrin-1 protein is not freely soluble but is associated with membranes and extracellular matrix. This distribution is consistent with netrin-1 acting as a short-range cue. Here we present a model whereby netrin-1 in the embryonic neural epithelium could act as a membrane-associated long-range cue. Netrin-1 is expressed in the adult by multiple types of neurons and by myelinating glia: oligodendrocytes in the CNS and Schwann cells in the PNS. In the white matter of the adult CNS, netrin-1 protein is absent from compact myelin but enriched in periaxonal myelin at the interface between axons and oligodendrocytes. This distribution suggests that in the adult nervous system netrin-1 may function to mediate cell-cell interactions. Furthermore, netrin receptor expression persists in neurons following injury, raising the possibility that netrin-1 may influence axonal regeneration.
Interaction of myc-associated zinc finger protein with DCC, the product of a tumor-suppressor gene, during the neural differentiation of P19 EC cells
2001, Biochemical and Biophysical Research Communications
Expression of the DCC ( $d$ eleted in $c$ olorectal $c$ ancer) protein is strongly induced during the neural differentiation of mouse P19 embryonal carcinoma (EC) cells that occurs when these cells are treated with retinoic acid (RA). Myc-associated zinc finger protein (MAZ) is a DNA-binding protein that is widely expressed and functions in human, mouse and hamster cells as an activator, an initiator or a terminator of transcription. However, the biological functions of MAZ remain elusive. We report here that MAZ associates with the cytoplasmic domain of the DCC protein in vivo and in vitro. Yeast two-hybrid assays confirmed this association. An immunofluorescence study demonstrated that DCC protein is expressed at elevated levels in neuron-like P19 EC cells, in particular in axons, in which the MAZ protein is also expressed. We found that MAZ was translocated from the nucleus to the cytoplasm during the RA-induced terminal differentiation of P19 EC cells with resultant loss of the ability of MAZ to bind to the ME1a1 site of the c-myc promoter. Taken together, our observations imply that the DCC protein might play a critical role as a signaling molecule in the regulation of the transcriptional activity of MAZ during the neural differentiation of P19 EC cells.

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cDCC (Chicken homologue to a gene deleted in colorectal carcinoma) is an epithelial adhesion molecule expressed in the basal cells and involved in epithelial-mesenchymal interaction

Neuron

Cell

Cell

Dev. Biol.

Neural cell adhesion molecule mediates contactdependent inhibition of growth of near-diploid mouse fibroblast cell line m5S/1M

J. Cell Biol.

The making of a feather: Homeoproteins, retinoids and adhesion molecules

BioEssays

Alteration in neural cell adhesion molecules during development of different regions of the nervous system

J. Neuro. Sci.

Expression of cell-adhesion molecules in embryonic induction. I. Morphogenesis of nestling feathers