Suppression Of β-catenin Nuclear Translocation By CGP57380 Decelerates Poor Progression And Potentiates Radiation-Induced Apoptosis in Nasopharyngeal Carcinoma

Wang, Weiyuan; Wen, Qiuyuan; Luo, Jianmin; Chu, Shuzhou; Chen, Lingjiao; Xu, Lina; Zang, Hongjing; Alnemah, Mohannad Ma; Li, Jinghe; Zhou, Jianhua; Fan, Songqing

doi:10.7150/thno.17665

Cited by 55 publications

(46 citation statements)

References 53 publications

(57 reference statements)

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“…Cell wound healing was performed as previously described . Cell migration was assessed by transwell assays.…”

Section: Methodsmentioning

confidence: 99%

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PLEK2 mediates metastasis and vascular invasion via the ubiquitin‐dependent degradation of SHIP2 in non‐small cell lung cancer

Deng

Zhou³

et al. 2019

Intl Journal of Cancer

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Metastasis is the leading cause of death for non‐small cell lung cancer (NSCLC) patients. However, how lung cancer cells invade blood vessels during metastasis remains unclear. Here, based on bioinformatics analyses, we found that PLEK2 might regulate NSCLC migration and vascular invasion. As little is known about the function of PLEK2 in NSCLC, we aimed to clarify this. We demonstrated that PLEK2 was significantly upregulated in transforming growth factor beta 1 (TGF‐β1)‐treated NSCLC cells through ELK1 transcriptional activation, highly expressed in NSCLC tissues, and negatively correlated with NSCLC overall survival. Meanwhile, PLEK2 overexpression significantly promoted NSCLC epithelial‐to‐mesenchymal transition (EMT) and migration, human lung microvascular endothelial cells endothelial‐to‐mesenchymal transition (EndoMT), and the destruction of vascular endothelial barriers. Moreover, PLEK2 knockdown inhibited TGF‐β1‐induced EMT and EndoMT. Furthermore, PLEK2 was found to directly interact with SHIP2 and target it for ubiquitination and degradation in NSCLC cells. Next, we confirmed that SHIP2 overexpression inhibits NSCLC EMT, migration and invasion and showed that PLEK2 overexpression can activate SHIP2‐associated TGF‐β/PI3K/AKT signaling. Our results suggest that PLEK2 could be a novel prognostic marker and potential therapeutic target for NSCLC metastasis and vascular invasion.

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“…Cell wound healing was performed as previously described . Cell migration was assessed by transwell assays.…”

Section: Methodsmentioning

confidence: 99%

“…Cell wound healing was performed as previously described. 10 Cell migration was assessed by transwell assays. Briefly, 1 × 10 5 cells in serum-free RPMI-1640 were seeded on a membrane (8.0-μm pore size) inserted in the wells of a 24-well plate.…”

Section: Cell Wound Healing Migration and Invasion Assaysmentioning

confidence: 99%

PLEK2 mediates metastasis and vascular invasion via the ubiquitin‐dependent degradation of SHIP2 in non‐small cell lung cancer

Deng

Zhou³

et al. 2019

Intl Journal of Cancer

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“…Our previous study has demonstrated that β-catenin pathway was abnormally activated in NPC (including β-catenin, cyclin D1, c-Myc and MMP7), we found that these proteins were abnormally activated in NPC compared with non-cancerous nasopharyngeal mucosa, and patients with aberrant β-catenin expression and overexpression of cyclin D1, c-Myc and MMP7 might have worse survival outcome 3. Normally, due to lack of β-catenin in nucleus, lymphoid enhancer factor (LEF)/transcription factor (TCF) combine with other proteins and repress target genes, and thus inhibit cell proliferation.…”

Section: Introductionmentioning

confidence: 71%

“…Based on our previous study, β-catenin pathway was abnormally activated in NPC (including β-catenin, cyclin D1, c-Myc and MMP7), and patients with aberrant β-catenin expression and overexpression of cyclin D1, c-Myc and MMP7 might have worse survival outcome 3. As the important components of the canonical Wnt/β-catenin pathway, LEF/TCF are confirmed to be abnormal in many malignant tumours.…”

Section: Discussionmentioning

confidence: 95%

Expression of LEF1 and TCF1 (TCF7) proteins associates with clinical progression of nasopharyngeal carcinoma

Zhan

Feng

et al. 2019

J Clin Pathol

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AimsOur previous study has demonstrated that β-catenin pathway was abnormally activated in nasopharyngeal carcinoma (NPC). The purposes of the present study are to investigate whether the alterations of LEF1 and TCF1 (TCF7) proteins, the important components of the canonical Wnt/β-catenin pathway, are associated with clinicopathological features and prognostic implications.MethodsWe collected 391 cases of NPC, 53 non-cancerous control nasopharyngeal mucosa and 28 pairs of NPC and their matched metastases, detected expression of LEF1 and TCF1 (TCF7) proteins in these tissues by immunohistochemistry. ResultsResults showed that there were significantly increased expression of both LEF1 and TCF1 (TCF7) proteins and coexpression of LEF1 and TCF1 (TCF7) in NPC than these in non-cancerous nasopharyngeal mucosa (all p<0.001), as well as LEF1 and coexpression of LEF1 and TCF1 (TCF7) in matched metastasis NPCs than these in the primary NPCs (p=0.003 and p=0.014, respectively). In addition, expression of LEF1 and the coexpression of LEF1 and TCF1 (TCF7) proteins were positively correlated with lymph node metastasis (p=0.001 and p=0.020, respectively), advanced clinical stage (p<0.003 and p=0.027, respectively) and poor survival status of patients with NPC (p<0.001 and p=0.004, respectively). Moreover, multivariate Cox regression analysis identified that the positive expression of LEF1 was the independent poor prognostic factor for overall survival of patients with NPC (p<0.001).ConclusionsThe expression of LEF1 associated positively with TCF1 (TCF7) and clinical progression of NPC, and positive expression of LEF1 protein may act as valuable independent biomarker to predict poor prognosis for patients with NPC.

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“…Previous studies have reported that the Wnt/β-catenin pathway is related to cell development and proliferation [23][24][25]. Therefore, the present study considered the Wnt/β-catenin pathway as a target pathway for aspirin-induced apoptosis.…”

Section: Aspirin Inhibited the Canonical Wnt/β-catenin Pathway Of Tscmentioning

confidence: 97%

High Concentration of Aspirin Induces Apoptosis in Rat Tendon Stem Cells via Inhibition of the Wnt/β-Catenin Pathway

Wang

Tang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in clinical practice to relieve fever and pain. Aspirin, as a representative NSAID, has been widely used in the treatment of tendinopathy. Some reports have demonstrated that aspirin can induce apoptosis in cancer cells. However, evidence regarding aspirin treatment for tendinopathy, especially the effect of this treatment on tendon stem cells (TSCs), is lacking. Understanding the effect of aspirin on tendinopathy may provide a basis for the rational use of NSAIDs in clinical practice. The aim of our study was to determine whether aspirin induces apoptosis in rat TSCs via the Wnt/β-catenin pathway. Methods: First, we used flow cytometry and fluorescence to detect TSC apoptosis. Protein expression of the apoptosis-related caspase-3 pathway was investigated via western blot analysis. Next, we used western blotting to determine the effect of aspirin on the Wnt/β-catenin pathway. We used immunostaining to detect the levels of Bcl2, cleaved caspase-3, and P-β-catenin in the Achilles tendon. Finally, we used flow cytometry, fluorescence, and western blotting to investigate the aspirin-induced apoptosis of TSCs via the Wnt/β-catenin pathway. Results: Aspirin induced morphological apoptosis in rat TSCs via the mitochondrial/caspase-3 pathway and induced cellular apoptosis in the Achilles tendon. Apoptosis was partly reversed after adding the Wnt signaling activator Wnt3a and lithium chloride (LiCl, a GSK-3β inhibitor). Aspirin administration led to a dose-dependent increase in COX-2 expression. Apoptosis was promoted after adding the COX-2 inhibitor NS398. Conclusion: The Wnt/β-catenin pathway plays a vital role in aspirin-induced apoptosis by regulating mitochondrial/caspase-3 function. Elevating COX-2 levels may protect cells against apoptosis. More importantly, the results remind us to consider the apoptotic effect of aspirin on TSCs and tendon cells when aspirin is administered to treat tendinopathy. The relationship between the positive and negative effects of aspirin remains a subject for future study.

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Suppression Of β-catenin Nuclear Translocation By CGP57380 Decelerates Poor Progression And Potentiates Radiation-Induced Apoptosis in Nasopharyngeal Carcinoma

Cited by 55 publications

References 53 publications

PLEK2 mediates metastasis and vascular invasion via the ubiquitin‐dependent degradation of SHIP2 in non‐small cell lung cancer

PLEK2 mediates metastasis and vascular invasion via the ubiquitin‐dependent degradation of SHIP2 in non‐small cell lung cancer

Expression of LEF1 and TCF1 (TCF7) proteins associates with clinical progression of nasopharyngeal carcinoma

High Concentration of Aspirin Induces Apoptosis in Rat Tendon Stem Cells via Inhibition of the Wnt/β-Catenin Pathway

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