<scp>CDK</scp>
            1‐mediated
            <scp>BCL</scp>
            9 phosphorylation inhibits clathrin to promote mitotic Wnt signalling

Chen, Jianxiang; Rajasekaran, Muthukumar; Xia, Hongping; Kong, Shik Nie; Deivasigamani, Amudha; Sekar, Karthik; Gao, Hengjun; Swa#, Hannah L F; Gunaratne, Jayantha; Ooi, London Lucien; Xie, Tian; Hong, Wanjin; Hui, Kam M.

doi:10.15252/embj.201899395

Cited by 24 publications

(21 citation statements)

References 60 publications

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“…Interestingly, BCL9 belongs to a small subset of 1q genes that were also found to be overexpressed and upregulated in group D, a cancer group bearing 16q-loss and 1q-disomy. Indeed, other mechanism linking BCL9 to Wnt signaling have been described, such as the ability to inhibit clathrin-mediated degradation of LRP6 signalosome components [ 82 ].…”

Section: Discussionmentioning

confidence: 99%

Aberrations of Chromosomes 1 and 16 in Breast Cancer: A Framework for Cooperation of Transcriptionally Dysregulated Genes

Privitera

Barresi

Condorelli

2021

Cancers

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Derivative chromosome der(1;16), isochromosome 1q, and deleted 16q—producing arm-level 1q-gain and/or 16q-loss—are recurrent cytogenetic abnormalities in breast cancer, but their exact role in determining the malignant phenotype is still largely unknown. We exploited The Cancer Genome Atlas (TCGA) data to generate and analyze groups of breast invasive carcinomas, called 1,16-chromogroups, that are characterized by a pattern of arm-level somatic copy number aberrations congruent with known cytogenetic aberrations of chromosome 1 and 16. Substantial differences were found among 1,16-chromogroups in terms of other chromosomal aberrations, aneuploidy scores, transcriptomic data, single-point mutations, histotypes, and molecular subtypes. Breast cancers with a co-occurrence of 1q-gain and 16q-loss can be distinguished in a “low aneuploidy score” group, congruent to der(1;16), and a “high aneuploidy score” group, congruent to the co-occurrence of isochromosome 1q and deleted 16q. Another three groups are formed by cancers showing separately 1q-gain or 16q-loss or no aberrations of 1q and 16q. Transcriptome comparisons among the 1,16-chromogroups, integrated with functional pathway analysis, suggested the cooperation of overexpressed 1q genes and underexpressed 16q genes in the genesis of both ductal and lobular carcinomas, thus highlighting the putative role of genes encoding gamma-secretase subunits (APH1A, PSEN2, and NCSTN) and Wnt enhanceosome components (BCL9 and PYGO2) in 1q, and the glycoprotein E-cadherin (CDH1), the E3 ubiquitin-protein ligase WWP2, the deubiquitinating enzyme CYLD, and the transcription factor CBFB in 16q. The analysis of 1,16-chromogroups is a strategy with far-reaching implications for the selection of cancer cell models and novel experimental therapies.

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Section: Discussionmentioning

confidence: 99%

Aberrations of Chromosomes 1 and 16 in Breast Cancer: A Framework for Cooperation of Transcriptionally Dysregulated Genes

Privitera

Barresi

Condorelli

2021

Cancers

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“…In CAA, the up-regulated NNT-AS1 can compete with miR-485 to bind to B-cell CLL/lymphoma 9 protein (BCL9), thereby increasing the expression of BCL9 and promoting the proliferation, migration, and invasion of CCA cells [22]. BCL9 was found to be involved in the regulation of the Wnt/β-catenin pathway [49,50]. In addition, Zhang et al found in GC cells that NNT-AS1 can regulate the expression of sex-determining region Y-related high-mobility-group-box transcription factor 4 (SOX4) through sponging miR-142-5p, while knockdown of NNT-AS1 will reduce β-catenin, c-Myc, and Bcl-2 but enhance e-cadherin expression.…”

Section: Nnt-as1 and The Wnt Signaling Pathwaymentioning

confidence: 99%

The Role of Long Non-Coding RNA NNT-AS1 in Neoplastic Disease

Zhou

Duan

2020

Cancers

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Studies have shown that non-coding RNAs (ncRNAs), especially long non-coding RNAs (lncRNAs), play an important regulatory role in the occurrence and development of human cancer. Nicotinamide nucleotide transhydrogenase-antisense 1 (NNT-AS1) is a newly-discovered cytoplasmic lncRNA. Many studies have shown that it has abnormally-high expression levels in malignant tumors, but there are also a few studies that have reported low expression levels of NNT-AS1 in gastric cancer, breast cancer, and ovarian cancer. At present, the regulatory mechanism of NNT-AS1 as a miRNA sponge, which may be an important reason affecting tumor cell proliferation, invasion, metastasis, and apoptosis is being studied in-depth. In addition, NNT-AS1 has been found to be related to cisplatin resistance. In this review, we summarize the abnormal expression of NNT-AS1 in a variety of neoplastic diseases and its diagnostic and prognostic value, and we explain the mechanism by which NNT-AS1 regulates cancer progression by competing with miRNAs. In addition, we also reveal the correlation between NNT-AS1 and cisplatin resistance and the potential clinical applications of NNT-AS1.

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“…This Wnt signaling pathway, now referred to as Wnt-mediated stabilization of proteins (Wnt/STOP) also involves LRP co-receptors and DVL ( 10 , 18 , 19 , 20 , 21 ) and promotes cell division and growth ( 18 , 22 , 23 , 24 ). Wnt/STOP activity peaks at the G2/M transition of the cell cycle because of the kinases CDK14-16, which phosphorylate and activate LRP6, and CDK1, which, in turn, phosphorylates and recruits BCL9 to the mitotic LRP6 signalosome ( 22 , 25 ).…”

Section: Introductionmentioning

confidence: 99%

Wnt10b-GSK3β–dependent Wnt/STOP signaling prevents aneuploidy in human somatic cells

et al. 2020

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Wnt signaling is crucial for proper development, tissue homeostasis and cell cycle regulation. A key role of Wnt signaling is the GSK3β-mediated stabilization of β-catenin, which mediates many of the critical roles of Wnt signaling. In addition, it was recently revealed that Wnt signaling can also act independently of β-catenin. In fact, Wnt mediated stabilization of proteins (Wnt/STOP) that involves an LRP6-DVL–dependent signaling cascade is required for proper regulation of mitosis and for faithful chromosome segregation in human somatic cells. We show that inhibition of Wnt/LRP6 signaling causes whole chromosome missegregation and aneuploidy by triggering abnormally increased microtubule growth rates in mitotic spindles, and this is mediated by increased GSK3β activity. We demonstrate that proper mitosis and maintenance of numerical chromosome stability requires continuous basal autocrine Wnt signaling that involves secretion of Wnts. Importantly, we identified Wnt10b as a Wnt ligand required for the maintenance of normal mitotic microtubule dynamics and for proper chromosome segregation. Thus, a self-maintaining Wnt10b-GSK3β–driven cellular machinery ensures the proper execution of mitosis and karyotype stability in human somatic cells.

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CDK 1‐mediated BCL 9 phosphorylation inhibits clathrin to promote mitotic Wnt signalling

Cited by 24 publications

References 60 publications

Aberrations of Chromosomes 1 and 16 in Breast Cancer: A Framework for Cooperation of Transcriptionally Dysregulated Genes

Aberrations of Chromosomes 1 and 16 in Breast Cancer: A Framework for Cooperation of Transcriptionally Dysregulated Genes

The Role of Long Non-Coding RNA NNT-AS1 in Neoplastic Disease

Wnt10b-GSK3β–dependent Wnt/STOP signaling prevents aneuploidy in human somatic cells

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