Characterization of the E‐cadherin/catenin complex in colorectal carcinoma cell lines

El‐Bahrawy, Mona; Poulsom, S Richard; Rowan, Andrew; Tomlinson, Ian; Alison, Malcolm R.

doi:10.1111/j.0959-9673.2004.0371.x

Cited by 51 publications

(36 citation statements)

References 52 publications

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“…The colon carcinoma cell line SW620 was used because it expresses p53 and transcriptionally active b-catenin (Lamy et al, 2010;El-Bahrawy et al, 2004;Li et al, 2007). In agreement with the coimmunoprecipitation data, we did not observe an association between the 14-3-3s gene promoter and b-catenin in any cell line (Fig.…”

Section: Plakoglobin and P53 Interact In Both The Cytoplasm And Nucleussupporting

confidence: 86%

“…The human tongue squamous cell carcinoma cell line SCC9, plakoglobin-expressing SCC9, MCF-7, MCF-10-2A and SW620 cells have been described previously (El-Bahrawy et al, 2004;Aktary et al, 2010;Lam et al, 2009). The vulvar carcinoma cell line A431 was obtained from the American Type Culture Collection (ATCC, Manassas, VA), and was maintained in Dulbecco's Modified Eagle's Medium supplemented with 10% FBS, 1% glucose and 1% antibiotics.…”

Section: Cell Culture and Conditionsmentioning

confidence: 99%

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Plakoglobin interacts with the transcription factor p53 and regulates the expression of 14-3-3σ

Aktary

Kulak

Mackey

et al. 2013

Journal of Cell Science

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SummaryPlakoglobin (c-catenin), a constituent of the adherens junction and desmosomes, has signaling capabilities typically associated with tumor/metastasis suppression through mechanisms that remain undefined. To determine the role of plakoglobin during tumorigenesis and metastasis, we expressed plakoglobin in human tongue squamous cell carcinoma (SCC9) cells and compared the mRNA profiles of parental SCC9 cells and their plakoglobin-expressing transfectants (SCC9-PG). We detected several p53-target genes whose levels were altered upon plakoglobin expression. In this study, we identified the p53 regulated tumor suppressor 14-3-3s as a direct plakoglobin-p53 target gene. Coimmunoprecipitation experiments revealed that plakoglobin and p53 interact, and chromatin immunoprecipitation and electrophoretic mobility shift assays revealed that plakoglobin and p53 associate with the 14-3-3s promoter. Furthermore, luciferase reporter assays showed that p53 transcriptional activity is increased in the presence of plakoglobin. Finally, knockdown of plakoglobin in MCF-7 cells followed by luciferase assays confirmed that p53 transcriptional activity is enhanced in the presence of plakoglobin. Our data suggest that plakoglobin regulates gene expression in conjunction with p53 and that plakoglobin may regulate p53 transcriptional activity, which may account, in part, for the tumor/metastasis suppressor activity of plakoglobin.

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Section: Plakoglobin and P53 Interact In Both The Cytoplasm And Nucleussupporting

confidence: 86%

Section: Cell Culture and Conditionsmentioning

confidence: 99%

Plakoglobin interacts with the transcription factor p53 and regulates the expression of 14-3-3σ

Aktary

Kulak

Mackey

et al. 2013

Journal of Cell Science

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“…These findings confirmed the data that have been previously published by our and other research groups, indicating a controversial role of E-cadherin in CRC [4,[18][19][20] The expression changes detected for some of the other cadherin superfamily members, exhibiting a down-regulated (PCDH24) or upregulated (CDH3) expression in the tumor progression process from normal colorectal mucosa to colorectal adenoma and carcinoma, have been already observed by other authors [21,22], demonstrating the reliability of our bioinformatic analysis conditions. Based on previous reports evidencing that the lack of expression of cadherin genes is rarely due to gene mutations [23] and it is more frequently the consequence of epigenetic changes [24,25] we perfomed a methylation analysis of μ-protocadherin promoter region in colorectal adenomas/carcinomas and CRC cell lines.…”

Section: Discussionsupporting

confidence: 91%

Characterization of Clinical and Molecular Features Related to the Downregulated Expression of μ-Protocadherin in Colorectal Cancer

Benhattar¹

2014

J Carcinog Mutagen

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Mu-protocadherin is a membrane protein belonging to the cadherin superfamily that, as the other members, promotes inter-cellular adhesion and proliferation arrest. Notably, both these onco-suppressive activities are mediated by its capacity to inhibit the β-catenin signaling pathway, that is constitutively activated in colorectal cancer (CRC) and, not surprisingly, its expression undergoes a remarkable down-regulation in CRC, although this finding has been to date only achieved in a limited set of patients. Based on this premise, the aims of our study were: (1) to confirm the down-regulated expression of μ-protocadherin in a larger cohort of CRC patients; (2) to assess the possible relationship existing between the expression levels of this protein and the clinical-pathological parameters of the disease; (3) to identify the molecular mechanism underlying the decrease of its expression occuring in CRC.To address these issues, we developed a database containing more than one thousand CRC expression profiles, recovered by GEO (Gene Expression Omnibus) and supplied with a significant set of clinical information, that was subsequently used to perform a bioinformatic analysis of cadherin genes. A methylation analysis of μ-protocadherin gene promoter was also carried out, using the bisulfite pyro-sequencing procedure, in an independent series of CRC samples. The results obtained confirmed the down-regulation of μ-protocadherin expression in CRC, suggested a possible prognostic role for this alteration and indicated the promoter hyper-methylation of its gene as the responsible mechanism.

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“…To better understand the regulation of ASEF by APC in CRCs, we suppressed the expression of ASEF by RNA interference in CRC cell lines that retain full-length (SW48 and HCT116) or truncated (SW480) APC 31,32 and assessed CDC42 activation and tumorigenic potential. We established individual cell lines stably expressing each of two independent short hairpin RNAs (shRNA-1 and shRNA-2) targeting ASEF or a nontargeting control (shRNA-C) and assessed the amount of GTP-bound CDC42 by affinity precipitation.…”

Section: Asef Is a Candidate Tumor Suppressormentioning

confidence: 99%

Release of autoinhibition of ASEF by APC leads to CDC42 activation and tumor suppression

Mitin

Betts

Yohe

et al. 2007

Nat Struct Mol Biol

116

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Autoinhibition of the Rho guanine nucleotide exchange factor ASEF is relieved by interaction with the APC tumor suppressor. Here we show that binding of the armadillo repeats of APC to a 'core APC-binding' (CAB) motif within ASEF, or truncation of the SH3 domain of ASEF, relieves autoinhibition, allowing the specific activation of CDC42. Structural determination of autoinhibited ASEF reveals that the SH3 domain forms an extensive interface with the catalytic DH and PH domains to obstruct binding and activation of CDC42, and the CAB motif is positioned adjacent to the SH3 domain to facilitate activation by APC. In colorectal cancer cell lines, full-length, but not truncated, APC activates CDC42 in an ASEF-dependent manner to suppress anchorage-independent growth. We therefore propose a model in which ASEF acts as a tumor suppressor when activated by APC and inactivation of ASEF by mutation or APC truncation promotes tumorigenesis.The adenomatous polyposis coli (APC) protein is a negative regulator of the Wnt signaling pathway and promotes the phosphorylation and degradation of β-catenin 1 . The majority of colorectal cancers (CRCs) harbor C-terminally truncated forms of APC that retain the Nterminal coiled-coil domain and the highly conserved armadillo repeat region (APC Arm ) 2 and are unable to regulate the degradation of β-catenin 3 . Recent studies suggest that APC regulates cytoskeletal dynamics to influence cellular migration, cell division, polarization and adhesion, and it seems increasingly likely that deregulated cytoskeletal dynamics, together with enhancement of transcription by β-catenin, potentiate tumor formation and progression upon APC truncation. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptAPC may regulate cytoskeletal networks by binding to microtubules and to proteins implicated in reorganization of the actin cytoskeleton, such as the Rho effectors mDia and IQGAP1 and the Rho guanine nucleotide exchange factor (RhoGEF) 'APC-stimulated guanine nucleotide exchange factor' (ASEF, also called ARHGEF4) 4 . ASEF is a Dbl-family GEF that contains an Src-homology-3 (SH3) domain followed by the Dbl-homology (DH) and pleckstrinhomology (PH) domains characteristic of Dbl-family GEFs that specifically activate members of the Rho family of GTPases. DH and PH domains in Dbl proteins catalyze the exchange of GDP for GTP in Rho GTPases, allowing them to signal to downstream effectors 5 . ASEF is homologous to the Dbl proteins collybistin (also called PEM2) and SPATA13 (also called ASEF2), both of which have been shown to activate specifically CDC42 and not other Rhofamily GTPases 6,7 .Previous data suggest that ASEF exists in an autoinhibited form and is activated upon binding of APC Arm to the region termed the APC-binding region (ABR) 8 . Binding of APC Arm to the ABR stimulates activation of the Rho GTPase RAC1 by ASEF. Furthermore, truncation of the ABR is sufficient to relieve autoinhibition, rendering ASEF constitutively active. In addition, truncated, but not wild-...

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Characterization of the E‐cadherin/catenin complex in colorectal carcinoma cell lines

Cited by 51 publications

References 52 publications

Plakoglobin interacts with the transcription factor p53 and regulates the expression of 14-3-3σ

Plakoglobin interacts with the transcription factor p53 and regulates the expression of 14-3-3σ

Characterization of Clinical and Molecular Features Related to the Downregulated Expression of μ-Protocadherin in Colorectal Cancer

Release of autoinhibition of ASEF by APC leads to CDC42 activation and tumor suppression

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