IPO11 mediates βcatenin nuclear import in a subset of colorectal cancers

O'Brien, Siobhan; Steinhart, Zachary; Lin, Sichun; Hart, Traver; Moffat, Jason; Angers, Stéphane

doi:10.1083/jcb.201903017

Cited by 34 publications

(29 citation statements)

References 49 publications

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“…During the preparation of the manuscript, a report showing that Ipo11 mediates βcatenin nuclear import in some colorectal cancers has been published, indicating that Ipo11 is required for Wnt/βcatenin activation and that Ipo11 might belong to a group of oncogenes [31]. As a result, Ipo11 must have diverse roles even in opposite according to the context on the cell death and survival, and there are a lot to be revealed for understanding the full scope of Ipo11 activity.…”

Section: Discussionmentioning

confidence: 99%

Importin-11 is Essential for Normal Embryonic Development in Mice

Lee¹,

Rahman²,

Kim³

et al. 2020

Int. J. Med. Sci.

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Importin-11 (Ipo11) is a novel member of the human importin family of transport receptors (karyopherins), which are known to mediate the nucleocytoplasmic transport of protein and RNA cargos. Despite its role in the transport of protein, we found that knockout of Ipo11 nuclear import factor affects normal embryonic development and govern embryo-lethal phenotypes in mice. In this study, we for the first time produced a mouse line containing null mutation in Ipo11 gene utilized by gene trapping. The Ipo11-/-embryos showed an embryonic lethal phenotype. The Ipo11-/-embryos showed a reduced size at embryonic day 10.5 (E10.5) when compared with Ipo11 +/+ or Ipo11 +/-embryos and died by E11.5. Whereas Ipo11 +/-mice were healthy and fertile, and there was no detectable changes in embryonic lethality and phenotype when reviewed. In the X-gal staining with the Ipo11-/-or Ipo11 +/-embryos, strong X-gal staining positivity was detected systematically in the whole mount embryos at E10.5, although almost no X-gal positivity was detected at E9.5, indicating that the embryos die soon after the process of Ipo11 expression started. These results indicate that Ipo11 is essential for the normal embryonic development in mice.

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Section: Discussionmentioning

confidence: 99%

Importin-11 is Essential for Normal Embryonic Development in Mice

Lee¹,

Rahman²,

Kim³

et al. 2020

Int. J. Med. Sci.

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“…as a factor required for beta-catenin transport 50 . Regardless of the exact mechanisms enabling NUP93 to control beta-catenin import, our promoter-reporter assays indicated that NUP93 more strongly regulates the beta-catenin pathway, as compared to other pathways.…”

Section: Discussionmentioning

confidence: 99%

Nucleoporin-93 overexpression overcomes multiple nucleocytoplsamic trafficking bottlenecks to permit robust metastasis

Nataraj

Noronha

Lee³

et al. 2020

Preprint

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To identify genetic events driving breast cancer progression, we performed multi-omics integrated analyses that identified overexpression of nucleoporin-93, a nuclear pore component. Here we show that NUP93 overexpression enhances trans-endothelial migration and matrix invasion in vitro, along with metastasis in animal models. These findings were supported by analyses of naturally occurring activating NUP93 mutations and inactivating nephrotic syndrome mutations. Mechanistically, NUP93 activation enhanced the ultimate nuclear transport step shared by multiple signaling pathways, including TGF-beta/SMAD, EGF/ERK and TNF/NF-κB. Likewise, NUP93 can boost nuclear transport of beta-catenin, as well as elevate expression and inhibit degradation of this co-activator. The emerging addiction to nuclear transport exposes vulnerabilities of tumors overexpressing NUP93. Congruently, we report that myristoylated peptides corresponding to the nuclear translocation signals of SMAD and ERK inhibited growth and metastasis. Our study illuminates a previously unappreciated hallmark of advanced tumors, which derive benefit from unblocking a set of nucleocytoplasmic bottlenecks.

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“…However, the NLS identi ed in DLX3 was shown to be su cient for nuclear localization [31] and our study found that DLX3 can be imported by IPO7. Two kinds of ways may help DLX3 maintain its biological activity: passive diffusion of DLX3 to the nucleus may be su cient for regular cell activity; however, the requirements of high level of DLX3 in nucleus during the odontogenic differentiation of mDPCs may need additional DLX3 nuclear import provided by an active IPO7 mediated process [33]. In addition to NLSs, many cargos recognized by IPO7 have the speci c structures such as the proline-rich homeodomain [34], zinc ngers [35], the PAS domain [36], the leucine zipper domain [37,38] and the phosphorylated domain [39].…”

Section: Discussionmentioning

confidence: 99%

IPO7 Promotes Odontoblastic Differentiation of Mouse Dental Papilla Cells by Selectively Importing Odontogenic Transcription Factors

Zhang¹,

Zhang²,

Yuan³

et al. 2020

Preprint

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Background: An important biological process for dentin formation and mineralization is odontoblast differentiation, which is precisely governed by a series of transcription factors (TFs). Importin 7 (IPO7) is a member of the Karyopherin β-superfamily mediating nucleocytoplasmic transport of proteins. In this study, we aimed to study the mechanisms by which IPO7 participates in odontoblastic differentiation. Methods: The expression patterns of IPO7 was investigated by immunofluorescence staining. Besides, mouse dental papilla cells (mDPCs) were extracted and cultured. After silencing Ipo7 in mDPCs, odontoblastic differentiation and the effect on odontogenic TFs were evaluated. Using nuclear and cytoplasmic extraction and co-immunoprecipitation assay, we aimed to confirm that IPO7 imports some odontogenic transcriptions factors to promote odontoblastic differentiation.Results: We found that IPO7 was increasingly expressed from the pre-odontoblasts to mature odontoblasts from PN2 to PN9. IPO7 enhanced odontoblast differentiation in mDPCs and imported essential TFs for odontoblastic differentiation, such as Distal-less homeobox 3 (DLX3), Osterix (OSX), Krüppel-like factor 4 (KLF4) and P-SMAD1/5 except for RUNX2. Besides, only RUNX2 showed no obvious interaction with IPO7.Conclusion: In conclusion, our data demonstrated that IPO7 enhances odontoblast differentiation in mDPCs by selectively importing odontogenic TFs.

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IPO11 mediates βcatenin nuclear import in a subset of colorectal cancers

Cited by 34 publications

References 49 publications

Importin-11 is Essential for Normal Embryonic Development in Mice

Importin-11 is Essential for Normal Embryonic Development in Mice

Nucleoporin-93 overexpression overcomes multiple nucleocytoplsamic trafficking bottlenecks to permit robust metastasis

IPO7 Promotes Odontoblastic Differentiation of Mouse Dental Papilla Cells by Selectively Importing Odontogenic Transcription Factors

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