Identification of E2F1 as a positive transcriptional regulator for δ-catenin

Kim, Kwonseop; Oh, Minsoo; Ki, Hyunkyoung; Wang, Tao; Bareiss, Sonja K.; Fini, M. Elizabeth; Li, Dawei; Lü, Qun

doi:10.1016/j.bbrc.2008.02.069

Cited by 21 publications

(33 citation statements)

References 25 publications

(16 reference statements)

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“…However, when injecting intravenously, metastasis frequencies were increased; even so, this is statistically insignificant (Rv/C, metastatic tumor formed in one out of five mice; Rv/δ, two out of five mice). Similarly, when we analyzed four prostate cancer cell lines with different metastatic potential (CWR22Rv-1, DU145, PC3, LNCaP), we found no correlation between metastatic potential and δ-catenin overexpression [43]. When cells were injected intravenously through a tail vein, they tended to form skin tumors and metastasize to different internal organs, including brain, lung and kidneys, to different extents (Kim et al, unpublished data).…”

Section: Resultsmentioning

confidence: 99%

δ-Catenin promotes E-cadherin processing and activates β-catenin-mediated signaling: Implications on human prostate cancer progression

Kim

Yang

et al. 2012

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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δ-Catenin binds the juxtamembrane domain of E-cadherin and is known to be overexpressed in some human tumors. However, the functions of δ-catenin in epithelial cells and carcinomas remain elusive. We found that prostate cancer cells overexpressing δ-catenin show an increase in multi-layer growth in culture. In these cells, δ-catenin colocalizes with E-cadherin at the plasma membrane, and the E-cadherin processing is noticeably elevated. E-Cadherin processing induced by δ-catenin is serum-dependent and requires MMP- and PS-1/γ-secretase-mediated activities. A deletion mutant of δ-catenin that deprives the ability of δ-catenin to bind E-cadherin or to recruit PS-1 to E-cadherin totally abolishes the δ-catenin-induced E-cadherin processing and the multilayer growth of the cells. In addition, prostate cancer cells overexpressing δ-catenin display an elevated total β-catenin level and increase nuclear distribution, resulting in the activation of β-catenin/LEF-1-mediated transcription and their downstream target genes as well as androgen receptor-mediated transcription. Indeed, human prostate tumor xenograft in nude mice, which is derived from cells overexpressing δ-catenin, shows increased β-catenin nuclear localization and more rapid growth rates. Moreover, the metastatic xenograft tumor weights positively correlate with the level of 29 kD E-cadherin fragment, and primary human prostate tumor tissues also show elevated levels of δ-catenin expression and the E-cadherin processing. Taken together, these results suggest that δ-catenin plays an important role in prostate cancer progression through inducing E-cadherin processing and thereby activating β-catenin-mediated oncogenic signals.

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Section: Resultsmentioning

confidence: 99%

δ-Catenin promotes E-cadherin processing and activates β-catenin-mediated signaling: Implications on human prostate cancer progression

Kim

Yang

et al. 2012

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…It is interesting and also paradoxical that δ-catenin expression levels in cancer-derived cell lines are generally moderate or minimal [74,75]. Its overexpression in prostate cancer cells altered tumor suppressor E-cadherin and p120 ctn distribution at the cell–cell junction [73], disrupted the normal monolayer in cell culture [76] and promoted prostate tumorigenesis in mice [76].…”

Section: Challenges On Most Fronts Of Anticancer Effortsmentioning

confidence: 99%

Pro-Oncogenic and Anti-Oncogenic Pathways: Opportunities and Challenges of Cancer Therapy

2010

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Carcinogenesis is the uncontrolled growth of cells gaining the potential to invade and disrupt vital tissue functions. This malignant process includes the occurrence of ‘unwanted’ gene mutations that induce the transformation of normal cells, for example, by overactivation of pro-oncogenic pathways and inactivation of tumor-suppressive or anti-oncogenic pathways. It is now recognized that the number of major signaling pathways that control oncogenesis is not unlimited; therefore, suppressing these pathways can conceivably lead to a cancer cure. However, the clinical application of cancer intervention has not matched up to scientific expectations. Increasing numbers of studies have revealed that many oncogenic-signaling elements show double faces, in which they can promote or suppress cancer pathogenesis depending on tissue type, cancer stage, gene dosage and their interaction with other players in carcinogenesis. This complexity of oncogenic signaling poses challenges to traditional cancer therapy and calls for considerable caution when designing an anticancer drug strategy. We propose future oncology interventions with the concept of integrative cancer therapy.

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“…Furthermore, examination of human EST data bank revealed δ- catenin mRNA sequences in prostate, kidney, ovarian, brain, breast, and esophageal tumors. Altered expression of δ-catenin was associated with cancer formation [16, 25], and Pax6 enhanced δ-catenin expression in prostate cancer cells [26]. In this study, we demonstrate, for the first time, that Pax6(+5a) and Pax6(−5a) regulate δ-catenin expression in an isoform- and dose-sensitive manner, but δ-catenin also exerts a feedback suppression on Pax6 with important implications in cellular morphogenesis, apoptosis, and cancer.…”

Section: Introductionmentioning

confidence: 99%

Isoform- and dose-sensitive feedback interactions between paired box 6 gene and δ-catenin in cell differentiation and death

Zhang

Suter

et al. 2010

Experimental Cell Research

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Pax6, a mammalian homolog of the Drosophila paired box gene family member expressed in stem and progenitor cells, resides at the top of the genetic hierarchy in controlling cell fates and morphogenesis. While Pax6 activation can lead to mitotic arrest, premature neurogenesis, and apoptosis, the underlying molecular mechanisms have not been resolved. Here we report that either Pax6(+5a) or Pax6(−5a) was sufficient to promote, whereas their knockdown reduced the expression of δ-catenin (CTNND2), a neural specific member of the armadillo/β-catenin superfamily. Pax6(+5a) elicited stronger effects on δ-catenin than Pax6(−5a). Inducible Pax6(+5a) expression demonstrated a biphasic and dose-dependent regulation of δ-catenin expression and cell fates. A moderate upregulation of Pax6(+5a) promoted δ-catenin expression and induced neurite-like cellular protrusions, but increasing expression of Pax6(+5a) reversed these processes. Furthermore, sustained high expression of Pax6(+5a) triggered apoptosis as determined by the reduction of phospho-Bad, Bcl-2, survivin and procaspases, as well as the increases in Bax and cleaved poly(ADP-ribose) polymerase. Importantly, re-introducing δ-catenin by ectopic expression elicited a feedback suppression on Pax6(+5a) expression and reduced Pax6(+5a) induced apoptosis. Therefore, δ-catenin expression is not only controlled by Pax6, but it also provides a feedback suppression mechanism for their functional interactions with important implications in cellular morphogenesis, apoptosis, and cancer.

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Identification of E2F1 as a positive transcriptional regulator for δ-catenin

Cited by 21 publications

References 25 publications

δ-Catenin promotes E-cadherin processing and activates β-catenin-mediated signaling: Implications on human prostate cancer progression

δ-Catenin promotes E-cadherin processing and activates β-catenin-mediated signaling: Implications on human prostate cancer progression

Pro-Oncogenic and Anti-Oncogenic Pathways: Opportunities and Challenges of Cancer Therapy

Isoform- and dose-sensitive feedback interactions between paired box 6 gene and δ-catenin in cell differentiation and death

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