Nucleoporin 93 mediates β-catenin nuclear import to promote hepatocellular carcinoma progression and metastasis

Lin, Cen-Shan; Liang, Yuyi; Su, Shu-Guang; Zheng, Yinli; Yang, Xia; Jiang, Neng; Fu, Lingyi; Zhou, Jing; Zhang, Ying; Deng, Ruijie; Wang, Chunhua; Lu, Shi-Xun; Huang, Yuhua; Liu, Li‐Li; Zhang, Chao; Yun, Jing‐Ping

doi:10.1016/j.canlet.2021.11.001

Cited by 21 publications

(6 citation statements)

References 35 publications

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“…Notably, GLFG-containing Nup98 demonstrates notably stronger positive correlations with the central and nuclear basket FG Nups compared to those on the cytoplasmic side, further highlighting that the exploration of Nup98 extends into the nuclear basket with some regularity. Previous studies have reported that GLFG-containing Nup98 displays strong positive correlations with all three nuclear basket Nups: Nup50, Nup153, and TPR 35 , 76 , 77 . Furthermore, when evaluating the correlation between Nup98 and the nuclear basket Nups in all three dimensions (XY and R dimension), the correlation calculations reveal a positive correlation among all three nuclear basket Nups (Supplementary Table S6), while a positive relationship exists only between Nup98 and both Nup153 and Nup50, as determined by Pearson’s correlation coefficient (Supplementary Table S7).…”

Section: Resultsmentioning

confidence: 82%

Exploring Cellular Gateways: Unraveling the Secrets of Disordered Proteins within Live Nuclear Pores

Yang,

yu,

Tingey

et al. 2024

Preprint

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Understanding the spatial organization of nucleoporins (Nups) with intrinsically disordered domains within the nuclear pore complex (NPC) is crucial for deciphering eukaryotic nucleocytoplasmic transport. Leveraging high-speed 2D single-molecule tracking and virtual 3D super-resolution microscopy in live HeLa cells, we investigated the spatial distribution of all eleven phenylalanine-glycine (FG)-rich Nups within individual NPCs. Our study reveals a nuanced landscape of FG-Nup conformations and arrangements. Five FG-Nups are steadfastly anchored at the NPC scaffold, collectively shaping a central doughnut-shaped channel, while six others exhibit heightened flexibility, extending towards the cytoplasmic and nucleoplasmic regions. Intriguingly, Nup214 and Nup153 contribute to cap-like structures that dynamically alternate between open and closed states along the nucleocytoplasmic transport axis, impacting the cytoplasmic and nuclear sides, respectively. Furthermore, Nup98, concentrated at the scaffold region, extends throughout the entire NPC while overlapping with other FG-Nups. Together, these eleven FG-Nups compose a versatile, capped trichoid channel spanning approximately 270 nm across the nuclear envelope. This adaptable trichoid channel facilitates a spectrum of pathways for passive diffusion and facilitated nucleocytoplasmic transport. Our comprehensive mapping of FG-Nup organization within live NPCs offers a unifying mechanism accommodating multiple transport pathways, thereby advancing our understanding of cellular transport processes.

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Section: Resultsmentioning

confidence: 82%

Exploring Cellular Gateways: Unraveling the Secrets of Disordered Proteins within Live Nuclear Pores

Yang,

yu,

Tingey

et al. 2024

Preprint

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“…Recent research suggested ADAMTSL2 was a negative regulator of TGF-β in human cardiac broblasts, inhibiting myo broblast differentiation and probrotic properties (38). Nucleoporin 93 (NUP93) mediates b-catenin nuclear import to promote hepatocellular carcinoma progression and metastasis (39). MPP2 is a member of a family of membraneassociated proteins termed MAGUKs, which interact with the cytoskeleton and regulate cell proliferation (40).…”

Section: Discussionmentioning

confidence: 99%

A Novel Cancer-associated Fibroblasts-Related Gene Signature Based on Adjuvant Sorafenib Efficacy for Predicting Recurrence and Immunotherapy Response in Hepatocellular Carcinoma After Hepatectomy

Liang

Feng

et al. 2023

Preprint

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Background Due to its high recurrence rate, hepatocellular carcinoma (HCC) has a poor prognosis after hepatectomy. An effective model to predict postoperative recurrence and identify high-risk patients is essential. Recent studies have revealed the important role of cancer-associated fibroblasts (CAFs) in predicting HCC prognosis. However, the prognostic value of CAFs-related gene signature in HCC recurrence remains unknown. According to the BIOSTORM study, adjuvant sorafenib efficacy data may help to predict the recurrence in HCC. Therefore, we aimed to create a novel CAFs-related gene signature based on adjuvant sorafenib efficacy to predict HCC recurrence. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to obtain the transcriptomic gene expression profiles and corresponding clinical data of HCC patients. The CAFs-related genes based on adjuvant sorafenib efficacy were identified using EPIC and weighted gene co-expression network analysis (WGCNA) algorithm. Univariate and the least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to establish a novel risk model. Univariate and multivariate COX analyses were used to identify independent prognostic factors for disease-free survival (DFS), and a nomogram was developed. The CIBERSORT and ESTIMATE algorithms were used to assess the tumor microenvironment components. Tumor immune dysfunction and exclusion (TIDE) score was used to predict immunotherapy response. Results A novel risk model was created using ten CAFs-related genes based on adjuvant sorafenib efficacy (DCLRE1C, DDX11, MAP4K2, SHCBP1, ADAM12, PAQR4, BEND3, ADAMTSL2, NUP93 and MPP2). Survival analyses revealed that high-risk patients had worse DFS, and the risk model was found as an independent prognostic factor for DFS in both the training and validation groups. A novel nomogram combined with pathologic stage and risk score status was developed. In the high-risk group, the stromal and immune cell content was found significantly lower while the tumor purity was significantly higher. In addition, immune checkpoints genes were highly expressed in the high-risk group and a higher risk score may predict a better response to immunotherapy. Conclusions The novel risk model comprised of ten CAFs-related genes based on adjuvant sorafenib efficacy may accurately predict recurrence and immunotherapy response in HCC patients after hepatectomy.

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“…Wang showed that EZH2 promotes aerobic glycolysis and increases the growth in glioma cells via b-catenin signaling (31). LEF1, a major transcription factor of the Wnt pathway, has been reported to play a significant role in cancer progression, such as in T lymphocyte acute lymphoblastic leukemia, hepatocellular carcinoma, and glioma (32)(33)(34)(35). Liu reported that LEF1 is a key regulator of the necroptotic machinery, and knocking it down sensitized chronic lymphocytic leukemia cells to TNFa/zVAD-induced necroptosis (36).…”

Section: Discussionmentioning

confidence: 99%

A novel model based on necroptosis-related genes for predicting immune status and prognosis in glioma

Yuan

Jin²,

Chen³

et al. 2022

Front. Immunol.

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BackgroundGlioma is a highly aggressive brain cancer with a poor prognosis. Necroptosis is a form of programmed cell death occurring during tumor development and in immune microenvironments. The prognostic value of necroptosis in glioma is unclear. This study aimed to develop a prognostic glioma model based on necroptosis.MethodsA necroptosis-related risk model was constructed by Cox regression analysis based on The Cancer Genome Atlas (TCGA) training set, validated in two Chinese Glioma Genome Atlas (CGGA) validation sets. We explored the differences in immune infiltration and immune checkpoint genes between low and high risk groups and constructed a nomogram. Moreover, we compiled a third validation cohort including 43 glioma patients. The expression of necroptosis-related genes was verified in matched tissues using immunochemical staining in the third cohort, and we analyzed their relationship to clinicopathological features.ResultsThree necroptosis-related differentially expressed genes (EZH2, LEF1, and CASP1) were selected to construct the prognostic model. Glioma patients with a high risk score in the TCGA and CGGA cohorts had significantly shorter overall survival. The necroptosis-related risk model and nomogram exhibited good predictive performance in the TCGA training set and the CGGA validation sets. Furthermore, patients in the high risk group had higher immune infiltration status and higher expression of immune checkpoint genes, which was positively correlated with poorer outcomes. In the third validation cohort, the expression levels of the three proteins encoded by EZH2, LEF1, and CASP1 in glioma tissues were significantly higher than those from paracancerous tissues. They were also closely associated with disease severity and prognosis.ConclusionsOur necroptosis-related risk model can be used to predict the prognosis of glioma patients and improve prognostic accuracy, which may provide potential therapeutic targets and a theoretical basis for treatment.

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Nucleoporin 93 mediates β-catenin nuclear import to promote hepatocellular carcinoma progression and metastasis

Cited by 21 publications

References 35 publications

Exploring Cellular Gateways: Unraveling the Secrets of Disordered Proteins within Live Nuclear Pores

Exploring Cellular Gateways: Unraveling the Secrets of Disordered Proteins within Live Nuclear Pores

A Novel Cancer-associated Fibroblasts-Related Gene Signature Based on Adjuvant Sorafenib Efficacy for Predicting Recurrence and Immunotherapy Response in Hepatocellular Carcinoma After Hepatectomy

A novel model based on necroptosis-related genes for predicting immune status and prognosis in glioma

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