Making heads or tails – the emergence of <i>capicua</i> (<i>CIC</i>) as an important multifunctional tumour suppressor

Wong, Derek F.; Yip, Stephen

doi:10.1002/path.5400

Cited by 20 publications

(18 citation statements)

References 87 publications

(148 reference statements)

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“…Among the unwanted potential outcomes of ATXN1 reduction is a decrease in the activity of the ATXN1 interactor CIC, a tumor suppressor. 26 ATXN1 interacts directly with CIC, modulating CIC’s transcriptional repressor activity. Importantly, loss of ATXN1 leads to a reduction in the level of CIC.…”

Section: Discussionmentioning

confidence: 99%

Antisense Oligonucleotide Therapeutic Approach for Suppression of Ataxin-1 Expression: A Safety Assessment

O’Callaghan

Hofstra

Handler

et al. 2020

Molecular Therapy - Nucleic Acids

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Spinocerebellar ataxia type 1 (SCA1) is a lethal, autosomal dominant neurodegenerative disease caused by a polyglutamine expansion in the ATAXIN-1 (ATXN1) protein. Preclinical studies demonstrate the therapeutic efficacy of approaches that target and reduce Atxn1 expression in a non-allele-specific manner. However, studies using Atxn1 −/− mice raise cautionary notes that therapeutic reductions of ATXN1 might lead to undesirable effects such as reduction in the activity of the tumor suppressor Capicua (CIC), activation of the protease β-secretase 1 (BACE1) and subsequent increased amyloidogenic cleavage of the amyloid precursor protein (APP), or a reduction in hippocampal neuronal precursor cells that would impact hippocampal function. Here, we tested whether an antisense oligonucleotide (ASO)-mediated reduction of Atxn1 produced unwanted effects involving BACE1, CIC activity, or reduction in hippocampal neuronal precursor cells. Notably, no effects on BACE1, CIC tumor suppressor function, or number of hippocampal neuronal precursor cells were found in mice subjected to a chronic in vivo ASO-mediated reduction of Atxn1 . These data provide further support for targeted reductions of ATXN1 as a therapeutic approach for SCA1.

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Section: Discussionmentioning

confidence: 99%

Antisense Oligonucleotide Therapeutic Approach for Suppression of Ataxin-1 Expression: A Safety Assessment

O’Callaghan

Hofstra

Handler

et al. 2020

Molecular Therapy - Nucleic Acids

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“…Capicua, a known tumor suppressor and an evolutionarily conserved high-mobility group-box transcription factor, is also deleted in PC3-AR cells [30,31]. The gene CTNNA1, known to be truncated in patients with hereditary diffuse gastric cancer (HDGC), is another gene with a known oncogenic role deleted in PC3-AR cells.…”

Section: Resultsmentioning

confidence: 99%

Genomic Analyses of the Metastasis-derived LNCaP, VCaP, and PC3-AR Prostate Cancer Cell Lines

Sienkiewicz

Yang

2021

Preprint

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The lymph node metastasis-derived LNCaP, the bone metastasis-derived PC3 (skull), and VCaP (vertebral) cell lines are widely used preclinical models of human prostate cancer (CaP) and have been described in >19,000 publications. Here, we report on short-read whole-genome sequencing and genomic analyses of LNCaP, VCaP, and PC3 cells stably transduced with WT AR (PC3-AR) . LNCaP cells are composed of multiple subpopulations, which results in non-integral copy number states and a high mutational load when the data is analyzed in bulk. All three cell lines contain pathogenic mutations and homozygous deletions in genes involved in DNA mismatch repair, along with deleterious mutations in cell-cycle, Wnt signaling, and other cellular processes. Furthermore, LNCaP cells contain a missense mutation in a well-known CaP hotspot of TP53, whereas both PC3-AR and VCaP have truncating mutations in TP53 and do not express p53 protein. In addition, we detect the signatures of chromothripsis of the q arms of chromosome 5 in both PC3-AR and VCaP cells, strengthening the association of TP53 inactivation with chromothripsis reported in other systems. Our work provides a resource for genetic, genomic, and biological studies employing these commonly-used prostate cancer cell lines.

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“…It is worthy to note that ERK could indirectly promote ETS expression by regulating CIC, a tumor suppressor in various cancers, including HCC. CIC repression on PEA3 sub-group genes (ETV1, ETV4, and ETV5) is relieved following ERK phosphorylation ( 54 ).…”

Section: The Regulatory Mechanism Underlying E-twenty-six Family In Hmentioning

confidence: 99%

The E-Twenty-Six Family in Hepatocellular Carcinoma: Moving into the Spotlight

et al. 2021

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Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality worldwide. Although therapeutic strategies have recently advanced, tumor metastasis and drug resistance continue to pose challenges in the treatment of HCC. Therefore, new molecular targets are needed to develop novel therapeutic strategies for this cancer. E-twenty-six (ETS) transcription family has been implicated in human malignancies pathogenesis and progression, including leukemia, Ewing sarcoma, gastrointestinal stromal tumors. Recently, increasing studies have expanded its great potential as functional players in other cancers, including HCC. This review focuses primarily on the key functions and molecular mechanisms of ETS factors in HCC. Elucidating these molecular details may provide novel potential therapeutic strategies for cancers.

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Making heads or tails – the emergence of capicua (CIC) as an important multifunctional tumour suppressor

Cited by 20 publications

References 87 publications

Antisense Oligonucleotide Therapeutic Approach for Suppression of Ataxin-1 Expression: A Safety Assessment

Antisense Oligonucleotide Therapeutic Approach for Suppression of Ataxin-1 Expression: A Safety Assessment

Genomic Analyses of the Metastasis-derived LNCaP, VCaP, and PC3-AR Prostate Cancer Cell Lines

The E-Twenty-Six Family in Hepatocellular Carcinoma: Moving into the Spotlight

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