Tissue transglutaminase expression is necessary for adhesion, metastatic potential and cancer stemness of renal cell carcinoma

Bağatur, Yeşim; Ilter-Akulke, Ayca Zeynep; Bihorac, Ajna; Erdem, Merve; Telci, Dilek

doi:10.1080/19336918.2017.1322255

Cited by 20 publications

(28 citation statements)

References 46 publications

(91 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S4A-C). The well-known clear cell renal cell carcinoma (CCRCC) CSC markers (ALDH1A1, CD44, CXCR4, DCLK1, CD105, ITGB1, NT5E, PIK3R1, PROM1 and THY1) [20][21][22][23][24][25][26][27] were displayed in the featurePlot to verify the expression in the identified CDRCCCSC cluster ( Supplementary Fig S5A, B). It was found that ALDH1A1, DCLK1, ITGB1 and PIK3R1 were also expressed in the identified CDRCC CSC cluster.…”

Section: Identification and Characterization Of Csc Populationmentioning

confidence: 99%

Identification of a novel cancer stem cell subpopulation that promotes progression of human fatal renal cell carcinoma by single-cell RNA-seq analysis

Pan¹,

Zhang²,

Xu³

et al. 2020

Int. J. Biol. Sci.

View full text Add to dashboard Cite

Background: Cancer stem cells (CSCs) are biologically characterized by self-renewal, multi-directional differentiation and infinite proliferation, inducing anti-tumor drug resistance and metastasis. In the present study, we attempted to depict the baseline landscape of CSC-mediated biological properties, knowing that it is vital for tumor evolution, anti-tumor drug selection and drug resistance against fatal malignancy. Methods: We performed single-cell RNA sequencing (scRNA-seq) analysis in 15208 cells from a pair of primary and metastatic sites of collecting duct renal cell carcinoma (CDRCC). Cell subpopulations were identified and characterized by t-SNE, RNA velocity, monocle and other computational methods. Statistical analysis of all single-cell sequencing data was performed in R and Python. Results: A CSC population of 1068 cells was identified and characterized, showing excellent differentiation and self-renewal properties. These CSCs positioned as a center of the differentiation process and transformed into CDRCC primary and metastatic cells in spatial and temporal order, and played a pivotal role in promoting the bone destruction process with a positive feedback loop in the bone metastasis microenvironment. In addition, CSC-specific marker genes BIRC5, PTTG1, CENPF and CDKN3 were observed to be correlated with poor prognosis of CDRCC. Finally, we pinpointed that PARP, PIGF, HDAC2, and FGFR inhibitors for effectively targeting CSCs may be the potential therapeutic strategies for CDRCC. Conclusion: The results of the present study may shed new light on the identification of CSCs, and help further understand the mechanism underlying drug resistance, differentiation and metastasis in human CDRCC.

show abstract

Section: Identification and Characterization Of Csc Populationmentioning

confidence: 99%

Identification of a novel cancer stem cell subpopulation that promotes progression of human fatal renal cell carcinoma by single-cell RNA-seq analysis

Pan¹,

Zhang²,

Xu³

et al. 2020

Int. J. Biol. Sci.

View full text Add to dashboard Cite

show abstract

“…TGM2 is a multifunctional protein with transamidating, deamidation, and GTPase activity, as well as enzyme-independent scaffolding functions. 45 It cross-links fibronectin and has scaffolding functions with integrin β1, both of which are associated with radiation resistance and stemness, 46,47 and has recently been proposed to promote neurogensis from neural stem cells in the adult brain. 48 Its inhibition improved survival in a glioma xenograft model 49 and it has been shown to be a prognostic indicator of shorter time to relapse after chemoradiotherapy.…”

Section: Irradiated Astrocytes Secrete Tgm2 In Vitro and In Vivo Aftementioning

confidence: 99%

The irradiated brain microenvironment supports glioma stemness and survival via astrocyte-derived Transglutaminase 2

Berg

Marques²,

Pantazopoulou

et al. 2020

Preprint

View full text Add to dashboard Cite

The tumor microenvironment plays an essential role in supporting glioma stemness and radioresistance; however, little is known about how the microenvironment responds to radiation. Here, we found that astrocytes, when pre-irradiated, increased stemness and survival of co-cultured glioma cells. Tumor-naïve brains increased reactive astrocytes in response to radiation, and mice subjected to radiation prior to implantation of glioma cells developed more aggressive tumors. We identified extracellular matrix derived from irradiated astrocytes as a major driver of this phenotype, and astrocyte-derived transglutaminase 2 (TGM2) as a promoter of glioma stemness and radioresistance. TGM2 inhibitors abrogated glioma stemness induced by irradiated astrocytes. TGM2 inhibition reduced survival of glioma cells in in vitro and ex vivo tumor models.These data suggest that irradiation of the brain results in the formation of a tumor-supportive microenvironment. Therapeutic targeting of radiation-induced, astrocyte-derived extracellular matrix proteins may enhance the efficacy of standard of care radiotherapy in glioma.

show abstract

“…It has been demonstrated that tissue transglutaminase, osteopontin, integrin α5, integrin αv, integrin β1, and integrin β3 bind to and are activated by fibronectin, and have been implicated in tumor cell proliferation, adhesion, migration, invasion, stemness, and resistance in a number of cancers, including RCC. The roles and importance of dimeric integrin receptor subunits vary and depend on cell types and microenvironments [18,19,21,22]. Dimeric integrin α5 and integrin β1 are common cell surface receptors of fibronectin [9,12,18].…”

Section: Discussionmentioning

confidence: 99%

Fibronectin Promotes Cell Growth and Migration in Human Renal Cell Carcinoma Cells

Wang

et al. 2019

IJMS

View full text Add to dashboard Cite

The prognostic and therapeutic values of fibronectin have been reported in patients with renal cell carcinoma (RCC). However, the underlying mechanisms of malignancy in RCC are not completely understood. We found that silencing of fibronectin expression attenuated human RCC 786-O and Caki-1 cell growth and migration. Silencing of potential fibronectin receptor integrin α5 and integrin β1 decreased 786-O cell ability in movement and chemotactic migration. Biochemical examination revealed a reduction of cyclin D1 and vimentin expression, transforming growth factor-β1 (TGF-β1) production, as well as Src and Smad phosphorylation in fibronectin-silenced 786-O and Caki-1 cells. Pharmacological inhibition of Src decreased 786-O cell growth and migration accompanied by a reduction of cyclin D1, fibronectin, vimentin, and TGF-β1 expression, as well as Src and Smad phosphorylation. In 786-O cells, higher activities in cell growth and migration than in Caki-1 cells were noted, along with elevated fibronectin and TGF-β1 expression. The additions of exogenous fibronectin and TGF-β1 promoted Caki-1 cell growth and migration, and increased cyclin D1, fibronectin, vimentin, and TGF-β1 expression, as well as Src and Smad phosphorylation. These findings highlight the role of fibronectin in RCC cell growth and migration involving Src and TGF-β1 signaling.

show abstract

Tissue transglutaminase expression is necessary for adhesion, metastatic potential and cancer stemness of renal cell carcinoma

Cited by 20 publications

References 46 publications

Identification of a novel cancer stem cell subpopulation that promotes progression of human fatal renal cell carcinoma by single-cell RNA-seq analysis

Identification of a novel cancer stem cell subpopulation that promotes progression of human fatal renal cell carcinoma by single-cell RNA-seq analysis

The irradiated brain microenvironment supports glioma stemness and survival via astrocyte-derived Transglutaminase 2

Fibronectin Promotes Cell Growth and Migration in Human Renal Cell Carcinoma Cells

Contact Info

Product

Resources

About