δ-Catenin promotes prostate cancer cell growth and progression by altering cell cycle and survival gene profiles

Zeng, Yan; Abdallah, Agustin; Lu, Jianping; Wang, Tao; Chen, Yanhua; Terrian, David M.; Kim, Kwonseop; Lü, Qun

doi:10.1186/1476-4598-8-19

Cited by 50 publications

(55 citation statements)

References 34 publications

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“…Indeed, in independent work, exogenous ␦-catenin expression resulted in limited cell death in NIH 3T3 cells (61). Conversely, however, ␦-catenin has been reported to have prosurvival activities in prostate adenocarcinoma cells (43) and elicited feedback suppression of Pax6-induced apoptosis in HeLa cells (62). In our present study employing a cell death ELISA method, we did not observe significant increases or decreases in chromatin breakage upon ␦-catenin expression (supplemental Fig.…”

Section: Apoptosis or Programmed Cell Death Is A Physiologicallymentioning

confidence: 99%

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Caspase-3 Cleavage Links δ-Catenin to the Novel Nuclear Protein ZIFCAT

Tonthat

Lee

et al. 2011

Journal of Biological Chemistry

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␦-Catenin is an Armadillo protein of the p120-catenin subfamily capable of modulating cadherin stability, small GTPase activity, and nuclear transcription. From yeast twohybrid screening of a human embryonic stem cell cDNA library, we identified ␦-catenin as a potential interacting partner of the caspase-3 protease, which plays essential roles in apoptotic as well as non-apoptotic processes. Interaction of ␦-catenin with caspase-3 was confirmed using cleavage assays conducted in vitro, in Xenopus apoptotic extracts, and in cell line chemically induced contexts. The cleavage site, a highly conserved caspase consensus motif (DELD) within Armadillo repeat 6 of ␦-catenin, was identified through peptide sequencing. Cleavage thus generates an amino-terminal (residues 1-816) and carboxyl-terminal (residues 817-1314) fragment, each containing about half of the central Armadillo domain. We found that cleavage of ␦-catenin both abolishes its association with cadherins and impairs its ability to modulate small GTPases. Interestingly, 817-1314 possesses a conserved putative nuclear localization signal that may facilitate the nuclear targeting of ␦-catenin in defined contexts. To probe for novel nuclear roles of ␦-catenin, we performed yeast two-hybrid screening of a mouse brain cDNA library, resolving and then validating interaction with an uncharacterized KRAB family zinc finger protein, ZIFCAT. Our results indicate that ZIFCAT is nuclear and suggest that it may associate with DNA as a transcriptional repressor. We further determined that other p120 subfamily catenins are similarly cleaved by caspase-3 and likewise bind ZIFCAT. Our findings potentially reveal a simple yet novel signaling pathway based upon caspase-3 cleavage of p120-catenin subfamily members, facilitating the coordinate modulation of cadherins, small GTPases, and nuclear functions.

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Section: Apoptosis or Programmed Cell Death Is A Physiologicallymentioning

confidence: 99%

“…In amphibians, ␦-catenin exhibits a much wider expression pattern, reflected functionally in its above noted essential role in early development/gastrulation (36). From the perspective of human disease, abnormal expression of ␦-catenin is associated with the progression of several carcinomas, including those of the prostate, lung, and breast (42)(43)(44).…”

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confidence: 99%

Caspase-3 Cleavage Links δ-Catenin to the Novel Nuclear Protein ZIFCAT

Tonthat

Lee

et al. 2011

Journal of Biological Chemistry

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“…Initially, it was widely accepted that d-catenin is the only member of the p120ctn family that is expressed specifically in neurons, where it binds to PDZ domain proteins in the post-synaptic compartment. (18)(19)(20) Latterly, the critical role of d-catenin in the modulation of cellular morphogenesis was found.(21-24) Similar to p120ctn, d-catenin could bind to the junxtamembrane domain (JMD) of E-cadherin (16,25) and regulate cadherin-cytoskeletal connections indirectly through functional interactions with Rho GTPases. (26) …”

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confidence: 99%

“…(18)(19)(20) Latterly, the critical role of d-catenin in the modulation of cellular morphogenesis was found. (21)(22)(23)(24) Similar to p120ctn, d-catenin could bind to the junxtamembrane domain (JMD) of E-cadherin (16,25) and regulate cadherin-cytoskeletal connections indirectly through functional interactions with Rho GTPases. (26) It has become clear that d-catenin is expressed in a variety of cancer tissues, including prostate, breast and esophageal tumors.…”

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Upregulation of δ‐catenin is associated with poor prognosis and enhances transcriptional activity through Kaiso in non‐small‐cell lung cancer

et al. 2010

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d-Catenin is the only member of the p120 catenin (p120ctn) subfamily that its primary expression is restricted to the brain. Since d-catenin is upregulated in human lung cancer, the effects of d-catenin overexpression in lung cancer still need to be clarified. Immunohistochemistry was performed to investigate the expression of d-catenin and Kaiso, a d-catenin-binding transcription factor, in 151 lung cancer specimens. A correlation between cytoplasmic d-catenin and Kaiso expression was also associated with high TNM stage, lymph node metastases and poor prognosis. Co-immunoprecipitation assay confirmed the interactions of d-catenin and Kaiso in lung cancer cells. In addition, gene transfection and RNAi technology were used to demonstrate that increased d-catenin expression was promoted, whereas its knockdown suppressed its lung cancer invasive ability. In addition, methylation-specific PCR and ChIP assay demonstrated that d-catenin could regulate MTA2 via Kaiso in a methylation-dependent manner, while it could regulate cyclin D1 and MMP7 expression through Kaiso in a sequence-specific manner. In conclusion, a d-catenin ⁄ Kaiso pathway exists in lung cancer cells. Increased d-catenin expression is critical for maintenance of the malignant phenotype of lung cancer, making d-catenin a candidate target protein for future cancer therapeutics. (Cancer Sci 2011; 102: 95-103) p 120 catenin (p120ctn) plays an important role in tumor progression and metastasis of non-small-cell lung cancer (NSCLC).(1,2) It is an Armadillo protein, which was first identified as a tyrosine kinase substrate implicated in cell transformation by Src.(3) It can bind to the juxtamembrane domain (JMD) of E-cadherin (4,5) where it modulates cell-cell adhesion by regulating cadherin turnover and stability at the cell surface.(6-8) In addition, p120ctn can bind directly with Kaiso, a transcription factor, (9) implicating a role for p120ctn in the regulation of transcriptional activity in addition to its cell-cell adhesion function.As a binding factor of p120ctn, Kaiso is a member of the BTB ⁄ POZ (Broad complex, Tramtrak, Bric à brac ⁄ Pox virus and zinc finger) subfamily of zinc finger proteins. It has the characteristic POZ domain at its amino-terminus where it facilitates Kaiso homodimerization and heterodimerization with diverse proteins, (10) while the zinc finger domain at the carboxyl terminal of Kaiso is responsible for DNA association.(11) Unlike any of the previously characterized POZ proteins, Kaiso could recognize both sequence-specific DNA consensus (KBS, TCCTGCNA) and methylated CpG-dinucleotides.(12,13) As a transcription repressor, (14) the majority of candidate Kaiso target genes identified thus far, that is, CDH1 (E-cadherin), MMP7, MTA2 and Wnt11, have been linked with development and ⁄ or cancer. (15) d-Catenin is an adhesive junction associated protein, (16,17) which is the only member of the p120ctn subfamily and its primary expression is restricted to the brain. Initially, it was widely accepted that d-catenin is the only m...

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Detection of CTC Clusters and a Dedifferentiated RNA‐Expression Survival Signature in Prostate Cancer

et al. 2018

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Rates of progression and treatment response in advanced prostate cancer are highly variable, necessitating non‐invasive methods to assess the molecular characteristics of these tumors in real time. The unique potential of circulating tumor cells (CTCs) to serve as a clinically useful liquid biomarker is due to their ability to inform via both enumeration and RNA expression. A microfluidic graphene oxide‐based device (GO Chip) is used to isolate CTCs and CTC clusters from the whole blood of 41 men with metastatic castration‐resistant prostate cancer. Additionally, the expression of 96 genes of interest is determined by RT‐qPCR. Multivariate analyses are conducted to determine the genes most closely associated with overall survival, PSA progression, and radioclinical progression. A preliminary signature, comprising high expression of stemness genes and low expression of epithelial and mesenchymal genes, potentially implicates an undifferentiated CTC phenotype as a marker of poor prognosis in this setting.

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δ-Catenin promotes prostate cancer cell growth and progression by altering cell cycle and survival gene profiles

Cited by 50 publications

References 34 publications

Caspase-3 Cleavage Links δ-Catenin to the Novel Nuclear Protein ZIFCAT

Caspase-3 Cleavage Links δ-Catenin to the Novel Nuclear Protein ZIFCAT

Upregulation of δ‐catenin is associated with poor prognosis and enhances transcriptional activity through Kaiso in non‐small‐cell lung cancer

Detection of CTC Clusters and a Dedifferentiated RNA‐Expression Survival Signature in Prostate Cancer

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