Glucose promotes epithelial‐mesenchymal transitions in bladder cancer by regulating the functions of YAP1 and TAZ

Shi, Li; Zhu, Hua; Chen, Hongde; Xia, Jianbo; Zhang, Fangyi; Xu, Ruoting; Lin, Qi

doi:10.1111/jcmm.15653

Cited by 19 publications

(14 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A positive association between high level of YAP1 and EMT-related genes, including vimentin and ZEB1 and stemness genes, at both transcriptomic and protein levels was observed [41,42]. In line with these findings, several studies demonstrated that YAP1 is a mediator of EMT and stemness in numerous types of carcinoma, including breast cancer [42][43][44][45].…”

Section: Discussionsupporting

confidence: 57%

Pirfenidone Reduces Epithelial–Mesenchymal Transition and Spheroid Formation in Breast Carcinoma through Targeting Cancer-Associated Fibroblasts (CAFs)

Cox

Sarafraz-Yazdi

et al. 2021

Cancers

View full text Add to dashboard Cite

The aim of this study was to assess the effects of pirfenidone (PFD) on promoting epithelial–mesenchymal-transition (EMT) and stemness features in breast carcinoma cells through targeting cancer-associated-fibroblasts (CAFs). Using The Cancer Genome Atlas (TCGA) database, we analyzed the association between stromal index, EMT, and stemness-related genes across 1084 breast cancer patients, identifying positive correlation between YAP1, EMT, and stemness genes in samples with a high-stromal index. We monitored carcinoma cell invasion and spheroid formation co-cultured with CAFs in a 3D microfluidic device, followed by exposing carcinoma cells, spheroids, and CAFs with PFD. We depicted a positive association between the high-stromal index and the expression of EMT and stemness genes. High YAP1 expression in samples correlated with more advanced EMT status and stromal index. Additionally, we found that CAFs promoted spheroid formation and induced the expression of YAP1, VIM, and CD44 in spheroids. Treatment with PFD reduced carcinoma cell migration and decreased the expression of these genes at the protein level. The cytokine profiling showed significant depletion of various EMT- and stemness-regulated cytokines, particularly IL8, CCL17, and TNF-beta. These data highlight the potential application of PFD on inhibiting EMT and stemness in carcinoma cells through the targeting of critical cytokines.

show abstract

Section: Discussionsupporting

confidence: 57%

Pirfenidone Reduces Epithelial–Mesenchymal Transition and Spheroid Formation in Breast Carcinoma through Targeting Cancer-Associated Fibroblasts (CAFs)

Cox

Sarafraz-Yazdi

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…[29][30][31] TAZ is highly expressed in many tumors and plays a key role in tumor cell proliferation, migration, stemness, and EMT. [32][33][34][35] We found that TAZ promotes the proliferation and invasion of GC cells and affects the expression of several EMT-related proteins. Moreover, we investigated TAZ regulation of VM-related markers (VE-cadherin, MMP2, and MMP9) and confirmed the correlation between TAZ and VM formation in vitro and in vivo, indicating its previously unrevealed role in promoting VM in GC.…”

Section: Discussionmentioning

confidence: 82%

TAZ promotes vasculogenic mimicry in gastric cancer through the upregulation of TEAD4

Zhang

Bai

Cheng

et al. 2022

J of Gastro and Hepatol

View full text Add to dashboard Cite

Background and Aim: Vasculogenic mimicry (VM) is a unique blood supply pattern in malignant tumors that is closely associated with metastasis and poor prognosis. The Hippo signaling effector TAZ is upregulated in several cancers, promoting cancer proliferation and metastasis. This study aimed to identify the function of TAZ and its regulatory mechanism in promoting VM in gastric cancer (GC). Methods: The expression of TAZ and TEAD4 and their correlations with overall survival and VM-related markers were analyzed in 228 cases of GC. The regulatory mechanism of TAZ and its interaction with TEAD4 in epithelial-mesenchymal transition (EMT) and VM were investigated in vitro and in vivo. Results: TAZ was highly expressed in GC samples and was associated with shorter patient survival time. TAZ expression was positively correlated with TEAD4 and VM in patients with GC. TAZ enhanced the migration and invasion capacity of GC cells through EMT in vitro and upregulated the expression of VM-associated proteins, including VEcadherin, MMP2, and MMP9, thus promoting VM formation. Overexpression of TAZ accelerated the growth of subcutaneous xenograft and promoted VM formation in vivo. Co-immunoprecipitation assays showed that TAZ can directly bind to TEAD4, and in vitro experiments showed that this binding mediates the function of TAZ in regulating EMT and VM formation in GC. Conclusions: TAZ promotes GC metastasis and VM by upregulating TEAD4 expression. Our findings expand the role of TAZ in VM and provide new theoretical support for the use of antiangiogenic therapy in the treatment of advanced GC.experiments. N. Z., X. L., and X. L. assisted in conducting the experiments and collecting data. X. Z. and B. S. designed the study and helped draft and edit the manuscript. R. C., F. L., and Y. L conducted and completed animal experiments.

show abstract

“…However, the development of metastases was not reported in these studies. When injected into the tail vein, T24 cells produced multiple lung or bone metastases [ 26 , 27 ]. Accordingly, there is some overlap when comparing the metastatic pattern of these cell lines in xenograft models to the uptake pattern of EVs observed in our study, especially with regard to the lungs.…”

Section: Discussionmentioning

confidence: 99%

Organ-Specific Uptake of Extracellular Vesicles Secreted by Urological Cancer Cells

Linxweiler

Kolbinger

Himbert

et al. 2021

Cancers

View full text Add to dashboard Cite

Extracellular vesicles (EVs) secreted by cancer cells have been shown to take a pivotal part in the process of local and systemic tumor progression by promoting the formation of a supportive local tumor microenvironment and preparing premetastatic niches in distant organ systems. In this study, we analyzed the organ-specific uptake of EVs secreted by urological cancer cells using an innovative in-vivo approach. EVs from benign and malignant prostate, kidney, and bladder cells were isolated using ultracentrifugation, fluorescence-labeled and injected intravenously in immunodeficient mice. After 12 or 24 h, the animals were sacrificed, their organs were harvested and analyzed for the presence of EVs by high-resolution fluorescence microscopy. Across all entities, EVs were taken up fast (12 h > 24 h), and EVs from malignant cells were taken up more efficiently than EVs from benign cells. Though not entirely organ-specific, EVs were incorporated in different amounts, depending on the entity (prostate: lung > liver > brain; kidney: brain > lung > liver; bladder: lung > liver > brain). EV uptake in other organs than lung, liver, brain, and spleen was not observed. Our results suggest a role of EVs in the formation of premetastatic niches and an organotropism in EV uptake, which have to be examined in more detail in further studies.

show abstract

Glucose promotes epithelial‐mesenchymal transitions in bladder cancer by regulating the functions of YAP1 and TAZ

Cited by 19 publications

References 34 publications

Pirfenidone Reduces Epithelial–Mesenchymal Transition and Spheroid Formation in Breast Carcinoma through Targeting Cancer-Associated Fibroblasts (CAFs)

Pirfenidone Reduces Epithelial–Mesenchymal Transition and Spheroid Formation in Breast Carcinoma through Targeting Cancer-Associated Fibroblasts (CAFs)

TAZ promotes vasculogenic mimicry in gastric cancer through the upregulation of TEAD4

Organ-Specific Uptake of Extracellular Vesicles Secreted by Urological Cancer Cells

Contact Info

Product

Resources

About