CSE1L promotes nuclear accumulation of transcriptional coactivator TAZ and enhances invasiveness of human cancer cells

Nagashima, Shunta; Maruyama, Junichi; Honda, Kaori; Kondoh, Yasumitsu; Osada, Hiroyuki; Nawa, Makiko; Nakahama, Ken-ichi; Ishigami‐Yuasa, Mari; Kagechika, Hiroyuki; Sugimura, Haruhiko; Iwasa, Hiroaki; Arimoto-Matsuzaki, Kyoko; Nishina, Hiroshi; Hata, Yoshinobu

doi:10.1016/j.jbc.2021.100803

Cited by 14 publications

(7 citation statements)

References 36 publications

(2 reference statements)

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“…In comparison, when individually depleting the other karyopherin-β type NTRs involved in import, including two of the three biportins, or the full set of importin α subtypes, only a slight reduction of YAP and TAZ nuclear localization was observable upon elimination of importin αs KPNA1, KPNA2, and KPNA7. This is consistent with earlier reports [45,157] implicating these importin α subtypes in YAP nuclear localization based on observed interactions (Section 3.2). Intriguingly, YAP, in return, controlled localization and function of importin 7: depletion of YAP or inhibition of the importin 7-YAP interaction by mechanical cues decreased importin 7 nuclear localization, whereas the MST1/2 inhibitor XMU-MP-1 had the opposite effect.…”

Section: Yap/yorkie Nuclear Import By a Karyopherin-β Type Ntrsupporting

confidence: 93%

“…The possibility of a direct involvement of classic import components in YAP/TAZ uptake was raised by pharmacological studies. Nagashima et al [157] found that a TAZ inhibitor, named TI-4, potently abrogated the nuclear accumulation of TAZ without affecting its phosphorylation. Searching for the underlying mechanism of this Hippo-independent effect, they identified CSE1L (exportin-2) as the major target of TI-4.…”

Section: Yap/taz-import Involving Importin α 331 Cse1l/importin αmentioning

confidence: 99%

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Nuclear Import and Export of YAP and TAZ

Kofler,

Kapus

2023

Cancers

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Yes-associated Protein (YAP) and its paralog Transcriptional Coactivator with PDZ-binding Motif (TAZ) are major regulators of gene transcription/expression, primarily controlled by the Hippo pathway and the cytoskeleton. Integrating an array of chemical and mechanical signals, they impact growth, differentiation, and regeneration. Accordingly, they also play key roles in tumorigenesis and metastasis formation. Their activity is primarily regulated by their localization, that is, Hippo pathway- and/or cytoskeleton-controlled cytosolic or nuclear sequestration. While many details of such prevailing retention models have been elucidated, much less is known about their actual nuclear traffic: import and export. Although their size is not far from the cutoff for passive diffusion through the nuclear pore complex (NPC), and they do not contain any classic nuclear localization (NLS) or nuclear export signal (NES), evidence has been accumulating that their shuttling involves mediated and thus regulatable/targetable processes. The aim of this review is to summarize emerging information/concepts about their nucleocytoplasmic shuttling, encompassing the relevant structural requirements (NLS, NES), nuclear transport receptors (NTRs, karyophererins), and NPC components, along with the potential transport mechanisms and their regulation. While dissecting retention vs. transport is often challenging, the emerging picture suggests that YAP/TAZ shuttles across the NPC via multiple, non-exclusive, mediated mechanisms, constituting a novel and intriguing facet of YAP/TAZ biology.

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Section: Yap/yorkie Nuclear Import By a Karyopherin-β Type Ntrsupporting

confidence: 93%

Section: Yap/taz-import Involving Importin α 331 Cse1l/importin αmentioning

confidence: 99%

Nuclear Import and Export of YAP and TAZ

Kofler,

Kapus

2023

Cancers

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“…RANBP17 biological network integration analysis found that XPO6, TNPO2, IPO9, XPO7, TNPO1, CSE1L have 3 functions. As of this time, XPO6, TNPO2, IPO9, XPO7, TNPO1 has not been reported in GBM, while CSE1L which is known to be involved in the recycling of importin α and as a biomarker of cancer malignancy, including formation, motility, and invasiveness [52]. Besides, we found 8 core upstream miRNA interact with RANBP17.…”

Section: Discussionmentioning

confidence: 67%

Comprehensive analysis reveals RANBP17 as a potential biomarker for prognosis and immunotherapy in glioblastoma

Tang¹,

Liu

Li³

et al. 2023

Preprint

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Objective: RAN binding protein 17 (RANBP17) gene is a member of the nuclear transport receptor imoprtin family, and have a close relation to the tumorigenesis. However, the role and mechanism of RANBP17 in glioblastoma (GBM) remains unclear. Here, we comprehensively explored the expression, prognostic value, epigenetic modification, immune filtration, tumor stemness, tumor heterogeneity, upstream miRNA and biological function of RANBP17 in GBM combined bioinformatics analysis with functional experiments in vitro. Methods: The expression of RANBP17 mRNA in GBM was analyzed by TIMER, UALCAN and CCGA databases. The prognostic value of RANBP17 was conducted by LinkedOmics, PrognoScan, and CGGA databases. Mutation status and type of RANBP17 was investigated by cBioportal database and COSMIC database, respectively. The RNA modification and DNA methylation of RANBP17 were analyzed by SangerBox and MethSurv databases. The relationships between RANBP17 expression and tumor heterogeneity, tumor stemness, and tumor immunity in human cancers were analyzed via the SangerBox, TISIDB and TIMER databases. Genes related to RANBP17 were screened by Linkedomics database, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were analyzed by DAVID and STRING database, and the protein-protein interaction (PPI) network was constructed by Cytoscape software. Furthermore, miRWalk, ENCORI and miRDB database was used to predict upstream miRNA of RANBP17. Moreover, the counting kit 8 (CCK-8) assay, flow cytometry, and transwell assays were conducted to evaluate the impact of RANBP17 on the proliferation, apoptosis, migration and invasion in U251 cell. Results: The expression of RANBP17 was downregulated and related to IDH mutation status, MGMT methylation status and 1p19q codeletion in GBM, which was associated with poor prognosis. RANBP17 was closely related to mRNA methylation genes, tumor heterogeneity and tumor stemness. GO and KEGG enrichment analysis indicated that RANBP17 was involved in neutrophil degranulation, response to estradiol and inflammatory response. Furthermore, the expression of RANBP17 was negatively correlated with B cell, CD4+ T cell, Macrophage, Neutrophil and dendritic cell, and positively correlated with tumor purity and CD8+ T cell. RANBP17 was also associated with hsa-miR-650, hsa-miR-361-5p, hsa-miR-421, hsa-miR-9-5p, hsa-miR-3612, hsa-miR-299-5p, hsa-miR-2115-3p and hsa-miR-19b-3p. Moreover, cell functional experiments in vitro demonstrated that overexpression of RANBP17 decreased cell proliferation, migration, invasion and facilitated apoptosis in GBM. Conclusions: These findings revealed that RANBP17 was anticipated to be a promising prognostic and immunotherapeutic biomarker in GBM.

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“…CSE1L overexpression was previously found to associate with the progression of a number of gastrointestinal cancers, including esophageal cancer, gastric cancer, hepatocellular carcinoma and CRC ( 1 , 2 , 44 , 45 ). Furthermore, CSE1L can promotes the nuclear distribution of the transcriptional coactivator with PDZ-binding motif to enhance the malignancy of human cancer tissues from osteosarcoma, glioma and lung cancer ( 46 ). Therefore, understanding the molecular mechanism underlying the effects of CSE1L may facilitate the optimization of cancer therapy ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

Butyrate supplementation regulates expression of chromosome segregation 1‑like protein to reverse the genetic distortion caused by p53 mutations in colorectal cancer

et al. 2022

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The chromosome segregation 1-like (CSE1L) protein, which regulates cellular mitosis and apoptosis, was previously found to be overexpressed in colorectal cancer (CRC) cells harboring mutations. Therefore, regulating CSE1L expression may confer chemotherapeutic effects against CRC. The gut microflora can regulate gene expression in colonic cells. In particular, metabolites produced by the gut microflora, including the short-chain fatty acid butyrate, have been shown to reduce CRC risk. Butyrates may exert antioncogenic potential in CRC cells by modulating p53 expression. The present study evaluated the association between CSE1L expression and butyrate treatment from two non-transformed colon cell lines (CCD-18Co and FHC) and six CRC cell lines (LS 174T, HCT116 p53 +/+ , HCT116 p53 −/− , Caco-2, SW480 and SW620). Lentiviral knockdown of CSE1L and p53, reverse transcription-quantitative PCR (CSE1L, c-Myc and p53), western blotting [CSE1L, p53, cyclin (CCN) A2, CCNB2 and CCND1], wound healing assay (cell migration), flow cytometry (cell cycle analysis) and immunofluorescence staining (CSE1L and tubulin) were adopted to verify the effects of butyrate on CSE1L-expressing CRC cells. The butyrate-producing gut bacteria Butyricicoccus pullicaecorum was administered to mice with 1,2-dimethylhydrazine-induced colon tumors before the measurement of CSE1L expression. The effects of B. pullicaecorum on CSE1L expression were then assessed by immunohistochemical staining for CSE1L and p53 in tissues from CRC-bearing mice. Non-cancerous colon cells with the R273H p53 mutation or CRC cells haboring p53 mutations were found to exhibit significantly higher CSE1L expression levels. CSE1L knockdown in HCT116 p53 −/− cells resulted in G 1 -and G 2 /M-phase cell cycle arrest. Furthermore, in HCT116 p53 −/− cells, CSE1L expression was already high at interphase, increased at prophase, peaked during metaphase before declining at cytokinesis but remained relatively high compared with that in HCT116 expressing wild-type p53. Significantly decreased expression levels of CSE1L were also observed in HCT116 p53 −/− cells that were treated with butyrate for 24 h. In addition, the migration of HCT116 p53 −/− cells was significantly decreased after CSE1L knockdown or butyrate treatment. Tumors with more intense nuclear p53 staining and weaker CSE1L staining were found in mice bearing DMH/DSS-induced CRC that were administered with B. pullicaecorum . Taken together, the results indicated that butyrate can impair CSE1L-induced tumorigenic potential. In conclusion, butyrate-producing microbes, such as B. pullicaecorum , may reverse the genetic distortion caused by p53 mutations in CRC by regulating CSE1L expression levels.

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CSE1L promotes nuclear accumulation of transcriptional coactivator TAZ and enhances invasiveness of human cancer cells

Cited by 14 publications

References 36 publications

Nuclear Import and Export of YAP and TAZ

Nuclear Import and Export of YAP and TAZ

Comprehensive analysis reveals RANBP17 as a potential biomarker for prognosis and immunotherapy in glioblastoma

Butyrate supplementation regulates expression of chromosome segregation 1‑like protein to reverse the genetic distortion caused by p53 mutations in colorectal cancer

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