The nuclear transporter importin-11 regulates the Wnt/β-catenin pathway and acts as a tumor promoter in glioma

Ni, Hongzao; Ji, Daofei; Li, Jing; Zhao, Zongren; Zuo, Jiandong

doi:10.1016/j.ijbiomac.2021.02.043

Cited by 5 publications

(4 citation statements)

References 37 publications

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“…In addition, LASS2 has been demonstrated to promote tumor cell apoptosis via ceramide [24,25], an effect that can be reduced when ceramide is converted into survival-promoting sphingosine 1-phosphate (S1P) by sphingosine kinase 1 (SPHK1) in glioblastoma [26,27]. Overexpression of LASS2 reduced the protein expression of SPHK1, MMP9, MMP2, Bcl-2, Vimentin, and N-cadherin while increasing that of TIMP2, Bax, activated caspase3, TNF-α, p53, and E-cadherin both in vitro and in vivo, suggesting that LASS2 suppresses the development and progression of glioma mainly by inhibiting tumor cell migration, invasion, and proliferation [28][29][30]. The inhibitory effect of LASS2 on subcutaneous xenograft growth further supports previous reports that LASS2 can function as a novel tumor-suppressing gene in glioma formation, progression, and metastasis.…”

Section: Discussionmentioning

confidence: 99%

LASS2 impairs proliferation of glioma stem cells and migration and invasion of glioma cells mainly via inhibition of EMT and apoptosis promotion

Zhao¹,

Fan²,

Ou³

et al. 2022

J. Cancer

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LAG1 longevity assurance homolog 2 (LASS2), a highly conserved transmembrane protein, has been reported in several cancer types. However, the roles of LASS2 in glioma biology remain elusive. In the present study, we investigated the expression of LAAS2 in human glioma tissues and the effects of LASS2 on glioma stem cell (GSC) proliferation. Roles of LASS2 in glioma cell migration and invasion were also researched both in vitro and in vivo. Our results demonstrated that the level of LASS2 is gradually reduced with the increase of glioma grade. The level of LASS2 is significantly lower in GSCs than in non GSCs, whereas LASS2 overexpression reduced the sphere formation and promoted the differentiation of CD133 + glioblastoma cells, as was indicated by reduced levels of CD133 and Nestin. In addition, LASS2 overexpression significantly reduced colony formation, migration, and invasion of glioma cells by promoting tumor cell apoptosis and inhibiting epithelial-mesenchymal transition (EMT). Overexpression of LASS2 inhibited U-87 MG cell-derived glioma xenograft growth in nude mice in a manner similar to in vitro. Our findings indicate that LASS2 can function as a suppressor of glioma growth, suggesting that modulation of LASS2 expression may contribute to a novel strategy for the management of glioma via inhibition of GSCs.

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Section: Discussionmentioning

confidence: 99%

LASS2 impairs proliferation of glioma stem cells and migration and invasion of glioma cells mainly via inhibition of EMT and apoptosis promotion

Zhao¹,

Fan²,

Ou³

et al. 2022

J. Cancer

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“…Wnt/β-catenin signaling pathway participates in the regulation of tumor cell growth and differentiation, and activation of Wnt/β-catenin signaling pathway can participate in the process and metastasis of glioma cells [19,20]. Studies revealed that inhibiting the Wnt/β-catenin signaling pathway can inhibit the proliferation and migration of glioma cells [21].…”

Section: Discussionmentioning

confidence: 99%

Effect of Licochalcone-A Combined with Rab23 Gene on Proliferation of Glioma U251 Cells

Dong

Cui

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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This research aimed to explore the effect of Licochalcone-A (LCA) combined with Rab23 gene on the proliferation, migration, and invasion of glioma U251 cells through the Wnt/β-catenin signaling pathway. The glioma U251 cell line was taken as the research object, and the Rab23 overexpression plasmid was constructed. According to the treatment method, U251 cells were rolled into blank control group (BC), Rab23 overexpression plasmid transfection group (Rab23), 25 μmol·L−1 LCA treatment group (LCA), and Rab23 overexpression plasmid transfection combined with 25 μmol·L−1 LCA treatment group (Rab23 + LCA). Subsequently, the ability of cell proliferation, migration, and invasion of each group was detected by methyl thiazolyl tetrazolium (MTT) assay, scratch healing test, and Transwell cell invasion test, respectively. Western blot was implemented to detect the expression differences of cell proliferation antigen Ki-67, apoptosis-related proteins Bcl-2 and Bax, and Wnt/β-catenin pathway-related proteins β-catenin, glycogen synthase kinase-3 (GSK3β), Axin2, and c-myc. The results showed the successful construction of Rab23 overexpression and stable transfection U251 cell line. After grouping and treatments, the cell proliferation, migration, and invasion ability of the Rab23 group, LCA group, and Rab23 + LCA group was substantially reduced relative to BC group ( P < 0.05 ). In addition, the cell proliferation, migration, and invasion ability of Rab23 + LCA group decreased relatively more significantly. The expression levels of Ki-67, Bcl-2, β-catenin, and c-myc in the Rab23, LCA, and Rab23 + LCA groups were greatly lower versus those of BC group. Moreover, the protein expression levels of Bax, GSK3β, and Axin2 were considerably increased ( P < 0.05 ), while the expression of protein in Rab23 + LCA group increased notably. These findings indicate that LCA combined with Rab23 gene can inhibit the proliferation, migration, and invasion of glioma U251 cells through the Wnt/β-catenin signaling and can promote cell apoptosis.

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“…Alternatively, Lgs/BCL9 has been suggested to escort beta-catenin into the nucleus where both proteins are anchored through interactions with Pygopus (Townsley et al, 2004). More recently, a role for importins was identified in glioma cells, where depletion of importin-11 resulted in a cytosolic shift in the nuclear-cytoplasmic beta-catenin distribution, suggesting importins could regulate nuclear bcatenin levels during tumorigenesis (Ni et al, 2021). Similarly, we report a SYS-1 interaction with importin b IMB-3 suggesting the hypothesis that conserved importin interactions may lead to SYS-1 nuclear translocation.…”

Section: Discussionmentioning

confidence: 99%

Nuclear localization and transactivation of SYS-1/β-catenin is the result of serial gene duplications and subfunctionalizations

Wolf

Adams-Phillips

Adams

et al. 2021

Preprint

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β-catenin is a multifunctional protein capable of mediating cell adhesion via E-cadherin and transactivation of target genes of the canonical Wnt signaling pathway. The nematode, C. elegans contains four paralogs of β-catenin which are highly specific in their functions. Though similar in overall structure, the four β-catenins are functionally distinct, each regulating different aspects of development. Of the four, SYS-1 is a key player in Wnt dependent asymmetric cell division (ACD). In ACD, a polarized mother will give rise to a daughter with high nuclear SYS-1 and another with low nuclear SYS-1. Despite sequence dissimilarity, SYS-1 shares a close structural resemblance with human β-catenin where it retains an unstructured amino-terminus (NTD) and 12 armadillo repeats. Using existing genome sequence data from several nematodes species, we find that the four β-catenin paralogs result from 3 sequential gene duplications and neofunctionalizations during nematode evolution. SYS-1, however, lacks an unstructured carboxyl-terminus (CTD) that is essential for human β-catenin transactivation processes. This work supports the hypothesis that SYS-1 compensated for the lack of CTD by acquiring novel transactivation domains with cryptic nuclear localization signals in the NTD and the first four armadillo repeats, as shown by transactivation assays in worms and yeast. Furthermore, SYS-1 regulatory domains are not localized to the NTD as in canonical β-catenin and instead spans the entire length of the protein. Truncating SYS-1 abolishes the classical SYS-1 nuclear asymmetry, resulting in daughter cells with symmetrical SYS-1 truncation localization. A screen for SYS-1 physical interactors followed by in vivo cell fate and SYS-1 localization analyses suggest that proper SYS-1 nuclear export is facilitated by XPO-1, while an interaction with IMB-3, an importin β-like protein, suggests import mechanisms. Interestingly, XPO-1 is especially required for lowering SYS-1 in the Wnt-unsignaled nucleus, suggesting a distinct mechanism for regulating asymmetric nuclear SYS-1. In summary, we provide insights on the mechanism of β-catenin evolution within nematodes and inform SYS-1 transactivation and nuclear transport.

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The nuclear transporter importin-11 regulates the Wnt/β-catenin pathway and acts as a tumor promoter in glioma

Cited by 5 publications

References 37 publications

LASS2 impairs proliferation of glioma stem cells and migration and invasion of glioma cells mainly via inhibition of EMT and apoptosis promotion

LASS2 impairs proliferation of glioma stem cells and migration and invasion of glioma cells mainly via inhibition of EMT and apoptosis promotion

Effect of Licochalcone-A Combined with Rab23 Gene on Proliferation of Glioma U251 Cells

Nuclear localization and transactivation of SYS-1/β-catenin is the result of serial gene duplications and subfunctionalizations

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