Complex cadherin expression in human prostate cancer cells

Bussemakers, M. J. G.; Bokhoven, Adrie van; Tomita, K.; Jansen, Cornelius F.J.; Schalken, Jack A.

doi:10.1002/(sici)1097-0215(20000201)85:3<446::aid-ijc23>3.0.co;2-b

Cited by 121 publications

(63 citation statements)

References 20 publications

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“…Adhesion could contribute to tumor suppression by physically joining cells, by facilitating other juxtacrine signaling events, or by binding and antagonizing the nuclear signaling function of b-catenin . Loss of E-cadherin is associated with poor prognosis in human prostate cancer, and thus may be linked to the progression rather than the initiation of the cancer (Bussemakers et al, 2000;Davies et al, 2000). In our model, the normal localization and strong expression of E-cadherin in the PIN-like lesions correlates with the absence of invasion or metastasis, and with the notion that the action of b-catenin is restricted to the initiation of the PIN lesions.…”

Section: Discussionsupporting

confidence: 54%

Stabilization of β-catenin induces lesions reminiscent of prostatic intraepithelial neoplasia, but terminal squamous transdifferentiation of other secretory epithelia

et al. 2002

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The present study documents that stabilization of bcatenin is su cient to induce lesions reminiscent of prostate intraepithelial neoplasia (PIN). Such lesions were present in all compound mutant mice and all prostate acini expressing stabilized b-catenin. High grade PIN-like lesions resembling early human prostate cancer were detected as early as 10 weeks of age. Surprisingly, stabilization of b-catenin in other secretory epithelia including salivary, preputial, harderian, and mammary glands induced extensive squamous metaplasia and keratinization associated with terminal di erentiation of the target cells, but failed to cause neoplastic transformation. Epidermal hyperplasia, hair follicle cysts, and odontomas were also observed. The prostatic lesions exhibited upregulation of c-myc, increased rate of cellular proliferation, loss of the Na-K-Cl co-transporter NKCC1, and expression of androgen receptor. Basal cell markers such as p63 and keratin 5 were not expressed by the masses of PIN-like lesions, but were present in small foci of proliferating b-catenin expressing basal cells. Our observations indicate that b-catenin stabilization is a crucial event for the initiation of PIN-like lesions, but induces squamous metaplasia rather than tumorigenesis in secretory epithelia other than the prostate.

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Section: Discussionsupporting

confidence: 54%

Stabilization of β-catenin induces lesions reminiscent of prostatic intraepithelial neoplasia, but terminal squamous transdifferentiation of other secretory epithelia

et al. 2002

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“…Disruption of the cadherin-catenin complex and the loss of the E-cadherin expression has been demonstrated in carcinomas arising in several tissues including prostate (Bussemakers et al, 2000), gastric (Shibata et al, 1996) and breast carcinomas (Pishvaian et al, 1999), and has been correlated with various pathologic and clinical features, such as tumor differentiation, proliferation and a poor patient prognosis (Hajra and Fearon, 2002).…”

Section: Discussionmentioning

confidence: 99%

Prediction of high risk Ewing's sarcoma by gene expression profiling

et al. 2004

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Ewing's sarcoma (ES) is the second most common primary malignant bone tumor in children and adolescents. Currently accepted clinical prognostic factors fail to classify ES patients' risk to relapse at diagnosis. We aimed to find a new strategy to distinguish between poor and good prognosis ES patients already at diagnosis. We analysed the gene expression profiles of 14 primary tumor specimens and six metastases from ES patients, using oligonucleotide microarray analysis. The over-expression of two genes was validated by quantitative PCR using the LightCycler system. We identified two distinct gene expression signatures distinguishing high-risk ES patients that are likely to progress from low-risk ES patients with a favorable prognosis of long-term progression-free survival. The microarray-based classification was superior to currently used prognostic parameters. Over-expressed genes in the poor prognosis patients included genes regulating the cell cycle and genes associated with invasion and metastasis, while among the downregulated genes were tumor suppressor genes and inducers of apoptosis. Our results indicate the existence of a specific gene expression signature of outcome in ES already at diagnosis, and provide a strategy to select patients who would benefit from risk-adapted improved therapy.

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“…The cell adhesion molecule, E-cadherin, serves a crucial role in inhibiting tumor cell migration and invasion by maintaining the cell-cell adhesion complex, and the inactivation of E-cadherin by gene deletion, promoter hypermethylation or proteolytic cleavage, renders tumor cells prone to a migratory and invasive phenotype due to the loss of cellular contact and polarity (41,42). Ectodomain cleavage of E-cadherin by several different proteases has been reported to yield an 80-kDa fragment known as sE-cad.…”

Section: Discussionmentioning

confidence: 99%

The Ectodomain Shedding of E-cadherin by ADAM15 Supports ErbB Receptor Activation

Najy

Day

2008

Journal of Biological Chemistry

165

211

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The zinc-dependent disintegrin metalloproteinases (a disintegrin and metalloproteinases (ADAMs) have been implicated in several disease processes, including human cancer. Previously, we demonstrated that the expression of a catalytically active member of the ADAM family, ADAM15, is associated with the progression of prostate and breast cancer. The accumulation of the soluble ectodomain of E-cadherin in human serum has also been associated with the progression of prostate and breast cancer and is thought to be mediated by metalloproteinase shedding. Utilizing two complementary models, overexpression and stable short hairpin RNA-mediated knockdown of ADAM15 in breast cancer cells, we demonstrated that ADAM15 cleaves E-cadherin in response to growth factor deprivation. We also demonstrated that the extracellular shedding of E-cadherin was abrogated by a metalloproteinase inhibitor and through the introduction of a catalytically inactive mutation in ADAM15. We have made the novel observation that this soluble E-cadherin fragment was found in complex with the HER2 and HER3 receptors in breast cancer cells. These interactions appeared to stabilize HER2 heterodimerization with HER3 and induced receptor activation and signaling through the Erk pathway, supporting both cell migration and proliferation. In this study, we provide evidence that ADAM15 catalyzes the cleavage of E-cadherin to generate a soluble fragment that in turn binds to and stimulates ErbB receptor signaling.The classic cadherins, epidermal cadherin (E-cadherin), neuronal cadherin (N-cadherin), and placental cadherin (P-cadherin), are type I transmembrane glycoproteins (1). The epidermal specific cadherin, E-cadherin, has five extracellular domain repeats that are involved in cell binding mediated by E-cadherin homotypic interaction (2). The intracellular domain consists of a conserved sequence that associates with ␤-, ␥-, and p120-catenins. The interaction of ␤-or ␥-catenin with ␣-catenin links E-cadherin to the cytoskeletal matrix to stabilize the adherens junction mediated by the homotypic E-cadherin complex (3). The involvement of E-cadherin in cell-cell interaction is well established in embryonic development, organ morphogenesis, tissue integrity, and wound healing (4). The disruption of E-cadherin by genetic mutation, promoter hypermethylation, or proteolytic cleavage leads to the loss of cell contact integrity as a consequence of adherens junction dissolution. E-cadherin disruption has been observed in multiple pathophysiological conditions, including inflammation and cancer (5). In fact, E-cadherin is considered to function as a metastasis suppressor due to its inhibition of cancer cell migration and invasion (6). Several proteases have been implicated in the extracellular cleavage of E-cadherin, including MMP3, MMP7, MT1-MMP, plasmin, kallikrein 7, and ADAM10. In addition, the cytoplasmic domain of E-cadherin is cleaved by caspace-3 and calpain (7,8). The ectodomain shedding of a stable 80-kDa soluble E-cadherin (sE-cad) 2 fragment has been sho...

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Complex cadherin expression in human prostate cancer cells

Cited by 121 publications

References 20 publications

Stabilization of β-catenin induces lesions reminiscent of prostatic intraepithelial neoplasia, but terminal squamous transdifferentiation of other secretory epithelia

Stabilization of β-catenin induces lesions reminiscent of prostatic intraepithelial neoplasia, but terminal squamous transdifferentiation of other secretory epithelia

Prediction of high risk Ewing's sarcoma by gene expression profiling

The Ectodomain Shedding of E-cadherin by ADAM15 Supports ErbB Receptor Activation

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