<i><scp>KLRC</scp>3</i>, a Natural Killer receptor gene, is a key factor involved in glioblastoma tumourigenesis and aggressiveness

Cheray, Mathilde; Bessette, Barbara; Lacroix, Aurélie; Mélin, Carole; Jawhari, Soha; Pinet, Sandra; Deluche, Élise; Clavère, P.; Durand, Karine; Sánchez‐Prieto, Ricardo; Jauberteau, Marie‐Odile; Battu, Serge; Lalloué, Fabrice

doi:10.1111/jcmm.12960

Cited by 21 publications

(18 citation statements)

References 30 publications

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“…This report prompted us to explore a mechanism of ADSL involvement in tumor cell aggressiveness independent of nucleotide synthesis. Indeed, in ADSL knockdown cells, expression of KLRC3, which was recently reported to be associated with glioblastoma aggressiveness [25], was shown to be reduced, and silencing of KLRC3 in endometrial cancer cells induced the same phenotype as that of ADSL, suggesting that the reduced tumor cell aggressiveness of ADSL knockdown cells was due to decreased expression of KLRC3.…”

Section: Discussionmentioning

confidence: 89%

“…As ADSL was shown to be associated with endometrial cancer cell aggressiveness, we searched for molecules involved in tumor aggressiveness. Among the top 25 molecules, we identified KLRC3, which has been described as a receptor on natural killer cells and was recently shown to be involved in glioblastoma tumorigenesis and aggressiveness [25]. We further examined the function of KLRC3 in (Fig.…”

Section: Klrc3 Expression Was Decreased In Adsl Knockdown Cellsmentioning

confidence: 99%

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Adenylosuccinate lyase enhances aggressiveness of endometrial cancer by increasing killer cell lectin-like receptor C3 expression by fumarate

Park

Ohshima

Nojima

et al. 2018

Laboratory Investigation

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Adenylosuccinate lyase (ADSL) is an enzyme that plays important roles in de novo purine synthesis. Although ADSL was reported to be upregulated in various malignancies, such as colorectal, breast, and prostate cancer, as well as gliomas, the mechanism by which elevated ADSL expression contributes to cancer has not been elucidated. We previously performed a shotgun proteomics analysis to characterize specific proteins associated with the properties of the aldehyde dehydrogenase (ALDH)-high cell population, which was reported to be involved in tumorigenic potential, and showed that ADSL expression is upregulated in the ALDH-high population of endometrial cancer. Here, we showed that ADSL is involved in endometrial cancer aggressiveness by regulating expression of killer cell lectin-like receptor C3 (KLRC3), which is a receptor expressed on natural killer cells. Immunohistochemical analysis indicated that ADSL expression increased as endometrioid carcinoma specimens became more poorly differentiated and higher degree of primary tumor progression. Knockdown of ADSL in endometrial cancer cells decreased cell proliferation, migration, and invasive capability, and caused the cells to adopt a more rounded shape. DNA microarray analysis and quantitative real-time PCR showed that KLRC3 expression was decreased in ADSL knockdown cells. Knockdown of KLRC3 in endometrial cancer cells resulted in the same phenotype as knockdown of ADSL. Moreover, fumarate, which could be produced by ADSL and was recently shown to be an oncometabolite, recovered KLRC3 expression in ADSL knockdown cells, suggesting that fumarate produced by ADSL could regulate KLRC3 expression. Our findings indicate that ADSL enhances cell proliferation, migration, and invasive capability through regulation of KLRC3 expression by fumarate.

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Section: Discussionmentioning

confidence: 89%

Section: Klrc3 Expression Was Decreased In Adsl Knockdown Cellsmentioning

confidence: 99%

Adenylosuccinate lyase enhances aggressiveness of endometrial cancer by increasing killer cell lectin-like receptor C3 expression by fumarate

Park

Ohshima

Nojima

et al. 2018

Laboratory Investigation

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“…For example, Shabo et al (49) reported an association between high TYROBP expression with skeletal and liver metastases as well as poor survival of breast cancer patients. Similarly, Cheray et al (50) implicated TYROBP in glioblastoma tumorigenesis and aggressiveness. In the present study, TYROBP overexpression was associated with poor survival of GC patients.…”

Section: Discussionmentioning

confidence: 92%

Identification of TYROBP and C1QB as Two Novel Key Genes With Prognostic Value in Gastric Cancer by Network Analysis

Jiang

Ding

et al. 2020

Front. Oncol.

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Background: Gastric cancer (GC) is the fifth most frequently diagnosed malignancy, and the third leading cause of tumor-related mortalities worldwide. Due to a high heterogeneity in GC, its treatment and prognosis are challenging, necessitating urgent identification of novel prognostic predictors for GC patients. Methods: We downloaded RNA sequence data, from the Cancer Genome Atlas and microarray data from Gene Expression Omnibus database, then identified common differentially-expressed genes (DEGs) between GC and normal gastric tissues across four datasets. We then used a combination of protein-protein interaction (PPI) network and weighted gene co-expression network analysis (WGCNA) to identify key genes with prognostic value in GC. Thereafter, we used quantitative real time polymerase chain reaction (qRT-PCR) to validate expression of the identified key genes in the Zhejiang University (ZJU) cohort. Finally, we evaluated the relationships between gene expression and immune factors, including immune cells and biomarkers of immunotherapy. Results: Among 426 common DEGs screened, 333 and 93 were upregulated and downregulated, respectively. PPI network and WGCNA successfully identified the top 30 hub genes, among which PTPRC, TYROBP, CCR1, CYBB, LCP2, and C1QB were common. Furthermore, TYROBP and C1QB were negatively associated with prognosis of GC patients, implying that they were key GC predictors. Interestingly, TYROBP and C1QB were positively correlated with predictive biomarkers for GC immunotherapy, including PD-L1 expression, CD8 + T cells infiltration, and EBV status. Conclusions: TYROBP and C1QB were identified as two novel key genes with prognostic value in GC by network analysis.

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“…However, CD133 cells isolated from primary patient tissue have been shown to generate tumours on implantation into rat brains also giving rise to CD133+ cells [ 41 ]. Other proteins such as CD44 and KLRC3 have also been investigated as markers of a CSC population, although recent evidence suggests that CD44 is an unreliable marker; cells expressing low levels of CD44 isolated from patient samples, also display CSC characteristics [ 42 , 63 , 64 ].…”

Section: Identification Of Cancer Stem Cells In An Array Of Cancermentioning

confidence: 99%

The Role of Autophagy and lncRNAs in the Maintenance of Cancer Stem Cells

Jahangiri

Ishola

Pucci

et al. 2021

Cancers

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Cancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and the detection, characterisation, and understanding of the regulatory landscape and cellular processes that govern their maintenance may pave the way to improving prognosis, selective targeted therapy, and therapy outcomes. In this review, we have discussed the characteristics of CSCs identified in various cancer types and the role of autophagy and long noncoding RNAs (lncRNAs) in maintaining the homeostasis of CSCs. Further, we have discussed methods to detect CSCs and strategies for treatment and relapse, taking into account the requirement to inhibit CSC growth and survival within the complex backdrop of cellular processes, microenvironmental interactions, and regulatory networks associated with cancer. Finally, we critique the computationally reinforced triangle of factors inclusive of CSC properties, the process of autophagy, and lncRNA and their associated networks with respect to hypoxia, epithelial-to-mesenchymal transition (EMT), and signalling pathways.

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KLRC3, a Natural Killer receptor gene, is a key factor involved in glioblastoma tumourigenesis and aggressiveness

Cited by 21 publications

References 30 publications

Adenylosuccinate lyase enhances aggressiveness of endometrial cancer by increasing killer cell lectin-like receptor C3 expression by fumarate

Adenylosuccinate lyase enhances aggressiveness of endometrial cancer by increasing killer cell lectin-like receptor C3 expression by fumarate

Identification of TYROBP and C1QB as Two Novel Key Genes With Prognostic Value in Gastric Cancer by Network Analysis

The Role of Autophagy and lncRNAs in the Maintenance of Cancer Stem Cells

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