The Wnt/β‐catenin/T‐cell factor 4 pathway up‐regulates high‐mobility group A1 expression in colon cancer

Bush, Bethany Marie; Brock, Ashton T.; Deng, Jiayue Amy; Nelson, Ronald A.; Sumter, Takita Felder

doi:10.1002/cbf.2876

Cited by 33 publications

(33 citation statements)

References 70 publications

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“…The Wnt/CTNNB1 signaling pathway participates in the human central nervous sytem, and in reproductive duct, breast, kidney, limb, placenta, hair and bone development. Furthermore, dysregulated expression of the components of the Wnt/CTNNB1 signaling pathway may induce embryo mortality or abnormal embryonic development (22). In addition, the Wnt/CTNNB1 signaling pathway is also associated with the renewal and differentiation of embryonic and multiple tissue stem cells.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the Wnt/CTNNB1 signaling pathway is also associated with the renewal and differentiation of embryonic and multiple tissue stem cells. Mucous epithelial cells require regular renewal and, therefore, intestinal tract stem/ancestral cells in the intestinal crypt regularly proliferate and differentiate (22). Following damage to, and the external stimulation of, mucous epithelial cells, stem/ancestral cells may proliferate and differentiate into numerous mucosal cells to maintain mucosal structural integrity (23).…”

Section: Discussionmentioning

confidence: 99%

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Wnt/catenin β1/microRNA 183 predicts recurrence and prognosis of patients with colorectal cancer

Chen

2018

Oncol Lett

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Abstract. The present study assessed the association between the Wnt/catenin β1 (CTNNB1)/microRNA (miR)183 signaling pathway and the recurrence and prognosis of colorectal cancer. The expression of Wnt, CTNNB1 and miR183 in primary colorectal cancer tissue was increased compared with that in the paracarcinoma tissue. Disease-free survival and overall survival were decreased in patients with colorectal cancer and increased miR183 expression compared with those in patients with colorectal cancer and decreased miR183 expression. The human colorectal cancer cell line HCT-116 was treated with 5 µM inhibitor of Wnt response (IWR-2) for 24 h to inhibit Wnt protein expression. Downregulating Wnt and CTNNB1 expression inhibited the viability of, and induced cell death and caspase 3 protein expression in, HCT-116 cells. The expression of BCL2 associated X protein and miR183 was increased, and cyclin D1 protein expression was suppressed, by the downregulation of Wnt and CTNNB1 expression in HCT-116 cells. Collectively, the results of the present study suggested that the Wnt/CTNNB1/miR183 signaling pathway may represent a promising biomarker for the recurrence and prognosis of colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Wnt/catenin β1/microRNA 183 predicts recurrence and prognosis of patients with colorectal cancer

Chen

2018

Oncol Lett

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“…Thus, it was unexpected to detect HMGA1 in terminally differentiated sensory neurons of calves latently infected with BoHV-1. Since HMGA1 is induced by the Wnt/␤-catenin signaling pathway and activates this pathway (18)(19)(20), HMGA1 may cooperate with ORF2 and ␤-catenin to maintain neuronal survival and normal neuronal functions during latency. The relevance of the other cellular genes differentially regulated during latency will require additional studies, and evaluation of their relevance was not in the scope of the present study.…”

Section: Discussionmentioning

confidence: 99%

“…The Super 8ϫ Top-Flash reporter accurately measures ␤-catenin-dependent transcription because when ␤-catenin is localized to the nucleus, it interacts with a TCF family member bound to the consensus site AGATCAAGG (reviewed in references 29 and 30). ␤-Catenin binding to TCF displaces bound corepressors and recruits transcriptional coactivators, thus stimulating the transcription of promoters containing TCF binding sites (18). HMGA1 stimulated ␤-catenin-dependent transcription more than 2-fold when 1 g of HMGA1 was used in the transfection but had little effect when a lower concentration (0.5 g) was used (Fig.…”

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confidence: 93%

“…The top gene induced in latently infected TG is the high-mobility group AT-hook 1 protein (HMGA1) (the level of expression of which was 2.8-fold times higher in latently infected TG than uninfected TG; P Ͻ 0.05). The HMGA1 gene encodes a nuclear protein that binds AT-rich DNA sequences, interacts with ␤-catenin, is induced by the Wnt/␤-catenin signaling pathway (18,19), and stimulates ␤-catenin-dependent transcription in cancer cells (20). Expression of another ␤-catenin regulator, frizzled homolog 8 (FZD8), was repressed 2.4-fold in the TG of latently infected calves compared to its expression in the TG of uninfected calves.…”

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confidence: 99%

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Potential Role for a β-Catenin Coactivator (High-Mobility Group AT–Hook 1 Protein) during the Latency-Reactivation Cycle of Bovine Herpesvirus 1

Zhu

Workman

Jones

2017

J Virol

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The latency-related (LR) RNA encoded by bovine herpesvirus 1 (BoHV-1) is abundantly expressed in latently infected sensory neurons. Although the LR gene encodes several products, ORF2 appears to mediate important steps during the latency-reactivation cycle because a mutant virus containing stop codons at the amino terminus of ORF2 does not reactivate from latency in calves. We recently found that the Wnt/␤-catenin signaling pathway is regulated during the BoHV-1 latency-reactivation cycle (Y. Liu, M. Hancock, A. Workman, A. Doster, and C. Jones, J Virol 90: 3148 -3159, 2016). In the present study, a ␤-catenin coactivator, highmobility group AT-hook 1 protein (HMGA1), was detected in significantly more neurons in the trigeminal ganglia of latently infected calves than in those of uninfected calves. Consequently, we hypothesized that HMGA1 cooperates with ORF2 and ␤-catenin to maintain latency. In support of this hypothesis, coimmunoprecipitation studies demonstrated that ORF2 stably interacts with a complex containing ␤-catenin and/or HMGA1 in transfected mouse neuroblastoma (Neuro-2A) cells. Confocal microscopy provided evidence that ORF2 was relocalized by HMGA1 and ␤-catenin in Neuro-2A cells. ORF2 consistently enhanced the ability of HMGA1 to stimulate ␤-catenin-dependent transcription, suggesting that interactions between ORF2 and a complex containing ␤-catenin and HMGA1 have functional significance. An ORF2 stop codon mutant, an ORF2 nuclear localization mutant, or a mutant lacking the 5 protein kinase A or C phosphorylation sites interfered with its ability to stimulate ␤-catenin-dependent transcription. Since the canonical Wnt/␤-catenin signaling pathway promotes neurogenesis (synapse formation and remodeling) and inhibits neurodegeneration, interactions between ORF2, HMGA1, and ␤-catenin may be important for certain aspects of the latency-reactivation cycle.IMPORTANCE The lifelong latency of bovine herpesvirus 1 (BoHV-1) requires that significant numbers of infected sensory neurons survive infection and maintain normal functions. Consequently, we hypothesize that viral products expressed during latency cooperate with neuronal factors to maintain latency. Our studies revealed that a ␤-catenin coactivator, high-mobility group AT-hook 1 protein (HMGA1), was readily detected in a subset of trigeminal ganglion neurons in latently infected calves but not in uninfected calves. A viral protein (ORF2) expressed in latently infected neurons interacted with ␤-catenin and HMGA1 in transfected cells, which resulted in the nuclear localization of ␤-catenin. This interaction correlated with the ability of ORF2 to stimulate the coactivator functions of HMGA1. These findings are significant

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miR‐214 activates TP53 but suppresses the expression of RELA, CTNNB1, and STAT3 in human cervical and colorectal cancer cells

Chandrasekaran

Sathyanarayanan

Karunagaran

2017

Cell Biochemistry & Function

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High Mobility Group AT-hook 1 (HMGA1) was identified as a target of miR-214 in human cervical and colorectal cancers (CaCx and CRC) in a previous study. While the expression of miR-214 remains suppressed, HMGA1 behaves as a potent oncogene and plays crucial roles in several aberrant signalling pathways by interacting with intermediates like RELA, CTNNB1, STAT3, and TP53 in CaCx and CRC. Hypothetically, miR-214 should be able to regulate the stabilization of some of these intermediates through the regulation of HMGA1. This was assessed by ectopically expressing miR-214 or complementarily, by inhibiting the expression of HMGA1. In promoter luciferase assays, miR-214 inhibited NF-κB and Wnt activities but elevated TP53 activity in cancer cells. Further, miR-214 suppressed the expression of HMGA1, RELA, CTNNB1, and STAT3 while elevating TP53 levels, similar to when small interfering RNA (siRNA) against HMGA1 was used, as revealed by Western blotting. It is suggested that poor expression of miR-214, commonly reported in CaCx and CRC tissues, may not only result in the sustained expression of HMGA1 but also that of RELA, CTNNB1, and STAT3, and a congruent suppression of TP53 during cancer initiation/progression. These several states are, however, reversed when miR-214 is reintroduced and could explain the tumour suppressive functions observed in earlier studies. Further studies are, however, required to reveal how microRNA-mediated regulation of HMGA1 expression may affect individual signalling pathways in CaCx and CRC. Current results reveal that miR-214 is not only able to regulate the expression of its direct target, HMGA1, but also that of a few signalling intermediates like TP53, RELA, CTNNB1, and STAT3, with which HMGA1 interacts. These intermediates play crucial roles in signalling pathways commonly deregulated in human CaCx and CRC. Hence, it is proposed that miR-214 might act as a tumour suppressor by regulating several aberrant signalling pathways through HMGA1. This knowledge has the potential to help design novel therapeutic strategies in CaCx and CRC.

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The Wnt/β‐catenin/T‐cell factor 4 pathway up‐regulates high‐mobility group A1 expression in colon cancer

Cited by 33 publications

References 70 publications

Wnt/catenin β1/microRNA 183 predicts recurrence and prognosis of patients with colorectal cancer

Wnt/catenin β1/microRNA 183 predicts recurrence and prognosis of patients with colorectal cancer

Potential Role for a β-Catenin Coactivator (High-Mobility Group AT–Hook 1 Protein) during the Latency-Reactivation Cycle of Bovine Herpesvirus 1

miR‐214 activates TP53 but suppresses the expression of RELA, CTNNB1, and STAT3 in human cervical and colorectal cancer cells

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