TGM2 inhibition attenuates ID1 expression in CD44-high glioma-initiating cells

Fu, Jun; Yang, Qun; Sai, Ke; Chen, Fu‐Rong; Pang, Jesse C.S.; Ng, Ho Keung; Kwan, Andy C.C.; Chen, Zhong Ping

doi:10.1093/neuonc/not079

Cited by 56 publications

(59 citation statements)

References 42 publications

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“…The inhibition of TGM2 may impair cell proliferation and induced apoptosis in gliomas [23], [24]. To validate the significance of differential expression of TGM2, a total of 82 meningioma samples were immunostained with a TGM2 antibody and quantified by microscopy under a 400X high power field (HPF) system (illustrated in Figure 2A and 2B).…”

Section: Resultsmentioning

confidence: 99%

Transglutaminase 2 Expression Is Increased as a Function of Malignancy Grade and Negatively Regulates Cell Growth in Meningioma

et al. 2014

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Most meningiomas are benign, but some clinical-aggressive tumors exhibit brain invasion and cannot be resected without significant complications. To identify molecular markers for these clinically-aggressive meningiomas, we performed microarray analyses on 24 primary cultures from 21 meningiomas and 3 arachnoid membranes. Using this approach, increased transglutaminase 2 (TGM2) expression was observed, which was subsequently validated in an independent set of 82 meningiomas by immunohistochemistry. Importantly, the TGM2 expression level was associated with increasing WHO malignancy grade as well as meningioma recurrence. Inhibition of TGM2 function by siRNA or cystamine induced meningioma cell death, which was associated with reduced AKT phosphorylation and caspase-3 activation. Collectively, these findings suggest that TGM2 expression increases as a function of malignancy grade and tumor recurrence and that inhibition of TGM2 reduces meningioma cell growth.

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Section: Resultsmentioning

confidence: 99%

Transglutaminase 2 Expression Is Increased as a Function of Malignancy Grade and Negatively Regulates Cell Growth in Meningioma

et al. 2014

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“…In contrast, activation of TGM2 has been suggested as a mediator for anti-apoptotic event in hypoxic tumour cells by inhibiting both caspase-3 activation and apoptosis induction (Jang et al, 2010). The increased expression of TGM2 in glioblastoma suggests a highly malignant glioma (Fu et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…TGM2 is conserved in the cytoplasm, nucleus and plasma membrane (Milakovic et al, 2004). TGM2 encodes for protein of extracellular matrix (ECM) molecules that are capable of catalysing protein cross-links between tumour cells and their microenvironments mediated by cell surface receptors (Fu et al, 2013). The reduced TGM2 level is a potential target in the treatment of highly metastatic cancer cells (Mehta et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Expression Profile of Genes Modulated by Aloe emodin in Human U87 Glioblastoma Cells

Haris

Ismail²,

Idris³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Glioblastoma, the most aggressive and malignant form of glioma, appears to be resistant to various chemotherapeutic agents. Hence, approaches have been intensively investigated to targeti specific molecular pathways involved in glioblastoma development and progression. Aloe emodin is believed to modulate the expression of several genes in cancer cells. We aimed to understand the molecular mechanisms underlying the therapeutic effect of Aloe emodin on gene expression profiles in the human U87 glioblastoma cell line utilizing microarray technology. The gene expression analysis revealed that a total of 8,226 gene alterations out of 28,869 genes were detected after treatment with 58.6 µg/ml for 24 hours. Out of this total, 34 genes demonstrated statistically significant change (p<0.05) ranging from 1.07 to 1.87 fold. The results revealed that 22 genes were up-regulated and 12 genes were down-regulated in response to Aloe emodin treatment. These genes were then grouped into several clusters based on their biological functions, revealing induction of expression of genes involved in apoptosis (programmed cell death) and tissue remodelling in U87 cells (p<0.01). Several genes with significant changes of the expression level e.g. SHARPIN, BCAP31, FIS1, RAC1 and TGM2 from the apoptotic cluster were confirmed by quantitative real-time PCR (qRT-PCR). These results could serve as guidance for further studies in order to discover molecular targets for the cancer therapy based on Aloe emodin treatment.

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“…Adjuvant chemotherapeutic reagents, as well as various combination therapies, have been extensively studied. Drugs used for combination therapies usually have clear pharmacokinetics, which leads to improved therapeutic efficiencies and tolerance, and reduces drug resistance and side effects (19,24,25). Due to their efficiency and few side effects, traditional Chinese medicines have been extensively studied in anti-cancer research.…”

Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin increases temozolomide efficacy in glioma cells by inducing autophagy

et al. 2015

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Abstract. Artemisinin, a powerful antimalarial medicine, is extracted from the Chinese herb, Artemisia annua L., and has the ability to inhibit the proliferation of cancer cells. Dihydroartemisinin (DHA), the major active metabolite of artemisinin, is able to inhibit the growth of a variety of types of human cancer. However, the effect of DHA on human glioma cells remains unclear. The aim of the present study was to investigate the effect of DHA on the proliferation of glioma cells, and whether DHA was able to enhance temozolomide (TMZ) sensitivity in vitro and in vivo. In total, 10 human glioma cell lines were used to analyze the growth inhibition ability of DHA by MTT assay. The typical autophagic vacuoles were monitored by the application of the autofluorescent agent, monodansylcadaverine. Western blotting was used to detect markers of apoptosis and autophagy, namely Caspase-3, Beclin-1 and LC3-B. The combination efficiency of DHA and TMZ was assessed in vitro and in vivo. The half maximal inhibitory concentration (IC 50 ) of DHA differed among the ten human glioma cell lines. The number of autophagic vacuoles was higher in DHA-treated SKMG-4 cells; this was highest of all cell lines analyzed. The expression of autophagy molecular markers, Beclin-1 and LC3-B, was increased following DHA treatment, while no significant alteration was detected in the expression of apoptotic marker Caspase-3. When combined with DHA, the IC 50 of TMZ decreased significantly in the four glioma cell lines analyzed. Furthermore, DHA enhanced the tumor inhibition ability of TMZ in tumor-burdened mice. The results of the present study demonstrated that DHA inhibited the proliferation of glioma cells and enhanced the tumor inhibition efficacy of TMZ in vitro and in vivo through the induction of autophagy.

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TGM2 inhibition attenuates ID1 expression in CD44-high glioma-initiating cells

Abstract: TGM2 regulates ID1 expression in glioma-initiating cell lines high in CD44. Targeting TGM2 could be an effective strategy to treat gliomas with high CD44 expression.

Cited by 56 publications

References 42 publications

Transglutaminase 2 Expression Is Increased as a Function of Malignancy Grade and Negatively Regulates Cell Growth in Meningioma

Transglutaminase 2 Expression Is Increased as a Function of Malignancy Grade and Negatively Regulates Cell Growth in Meningioma

Expression Profile of Genes Modulated by Aloe emodin in Human U87 Glioblastoma Cells

Dihydroartemisinin increases temozolomide efficacy in glioma cells by inducing autophagy

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