Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Epithelial Cell Adhesion Molecule or EpCAM is a well-known marker highly expressed in carcinomas and showing a strong correlation with poor cancer prognosis. While its name relates to its proposed function as a cell adhesion molecule, EpCAM has been shown to have various signalling functions. In particular, it has been identified as an important positive regulator of cell adhesion and migration, playing an essential role in embryonic morphogenesis as well as intestinal homeostasis. This activity is not due to its putative adhesive function, but rather to its ability to repress myosin contractility by impinging on a PKC signalling cascade. This mechanism confers EpCAM the unique property of favouring tissue plasticity. I review here the currently available data, comment on possible connections with other properties of EpCAM, and discuss the potential significance in the context of cancer invasion.
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PMID:EpCAM as Modulator of Tissue Plasticity. 3296 90

EpCAM has long been known as a cell surface protein highly expressed in carcinomas. It has since become one of the key cancer biomarkers. Despite its high fame, its actual role in cancer development is still controversial. Beyond a flurry of correlative studies, which point either to a positive or a negative link with tumour progression, there has been surprisingly few studies on the actual cellular mechanisms of EpCAM and on their functional consequences. Clearly, EpCAM plays multiple important roles, in cell proliferation as well as in cell adhesion and migration. The two latter functions, directly relevant for metastasis, are the focus of this review. We attempt here to bring together the available experimental data to build a global coherent view of EpCAM functions. We also include in this overview EpCAM2/Trop2, the close relative of EpCAM. At the core of EpCAM (and EpCAM2/Trop2) function stands the ability to repress contractility of the actomyosin cell cortex. This activity appears to involve direct inhibition by EpCAM of members of the novel PKC family and of a specific downstream PKD-Erk cascade. We will discuss how this activity can result in a variety of adhesive and migratory phenotypes, thus potentially explaining at least part of the apparent inconsistencies between different studies. The picture remains fragmented, and we will highlight some of the conflicting evidence and the many unsolved issues, starting with the controversy around its original description as a cell-cell adhesion molecule.
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PMID:EpCAM cellular functions in adhesion and migration, and potential impact on invasion: A critical review. 3297 80

E-cadherin, an epithelial cell-specific cell adhesion molecule, has both promoting and suppressing effects on tumor invasion and metastasis. It is often downregulated during cancer progression through gene deletion/mutation, transcriptional repression, or epigenetic silencing. We describe a novel regulatory switch to induce stimulus-dependent downregulation of mRNA encoding E-cadherin (CDH1 mRNA) in KRAS-mutated cancer cells. The regulatory switch consists of ZEB1 and oncogenic K-Ras, does not target the promoter region of CDH1, and requires an external cue to temporally downregulate E-cadherin expression. Its repressive effect is maintained as long as the external stimulus continues and is attenuated with cessation of the stimulus. Contextual external cues that turn this regulatory switch on include activation of protein kinase C or fibroblast growth factor signaling. The mode of action is distinct from that of EPCAM repression by ZEB1, which does not require an external cue. Thus, KRAS-mutated cancer cells acquire a novel mode of regulating E-cadherin expression depending on ZEB1, which could contribute to phenotypic plasticity of cancer cells during malignant progression.
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PMID:ZEB1 and oncogenic Ras constitute a regulatory switch for stimulus-dependent E-cadherin downregulation. 3306 45


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