Transglutaminase 3 protein modulates human esophageal cancer cell growth by targeting the NF-κB signaling pathway

Li, Wei; Zhang, Zhongmian; Zhao, Wenchao; Han, Ning

doi:10.3892/or.2016.4921

Cited by 20 publications

(10 citation statements)

References 43 publications

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“…Furthermore, low TGM3 expression is associated with poor overall survival [32]. There is also evidence for TGM3 to induce cell proliferation and migration in esophageal cancer by downregulating the NF-κB signaling pathway [33]. Genome-wide association study (GWAS) of 38.5 million SNPs and small indels identified TGM3 variant as a contributor to risk of basal cell carcinoma [34].…”

Section: Resultsmentioning

confidence: 99%

Significantly mutated genes and regulatory pathways in SCLC—a meta-analysis

et al. 2017

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Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers and demands effective targeted therapeutic strategies. In this meta-analysis study, we aim to identify significantly mutated genes and regulatory pathways to help us better understand the progression of SCLC and to identify potential biomarkers. Besides ranking genes based on their mutation frequencies, we sought to identify statistically significant mutations in SCLC with the MutSigCV software. Our analysis identified several genes with relatively low mutation frequency, including PTEN, as highly significant (p<0.001), suggesting these genes may play an important role in the progression of SCLC. Our results also indicated mutations in genes involved in the axon guidance pathways likely play an important role in SCLC progression. In addition, we observed that the mutation rate was significantly higher in samples with RB1 gene mutated when compared to samples with wild type RB1, suggesting that RB1 status has significant impact on the mutation profile and disease progression in SCLC.

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Section: Resultsmentioning

confidence: 99%

Significantly mutated genes and regulatory pathways in SCLC—a meta-analysis

et al. 2017

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“…As a molecular mecha-nism of TG3 repression, hypermethylation of CpG islands within the TGM3 promoter has been proposed [18]. Furthermore, TGM3 was shown as a putative tumour-suppressor gene in oesophageal cancer, in which its expression was downregulated and associated with tumour proliferation and migration [19,20]. Skin cancer is the most common type of cancer.…”

mentioning

confidence: 99%

Transglutaminase 3 is expressed in basal cell carcinoma of the skin

Smirnov¹,

Anemona²,

Montanaro³

et al. 2019

European Journal of Dermatology

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Transglutaminase 3 is expressed in basal cell carcinoma of the skin Background: Transglutaminase 3 (TG3) belongs to a family of Ca 2+dependent enzymes which catalyse protein crosslinking. TG3 is important for proper development of the skin and hair shaft, and knockout mice for the Tgm3 gene are sensitive to UVB-induced photodamage due to aberrations in cornified envelope formation. Loss of TG3 is reported in head and neck and oesophageal squamous cell carcinoma, yet, its expression in skin cancer has not been studied. Objectives: The aim of the present study was to analyse the expression pattern of TG3 in skin cancer. Materials and methods: TG3 expression was investigated based on immunohistochemical staining of a tissue micro-array of different types of skin cancer, as well as meta-analysis of public gene array data. Results: Our findings demonstrated that TG3 is normally expressed in spinous/granular layers of the epidermis, but is absent in melanocytes as well as melanoma samples. As expected, its expression was absent in poorly differentiated squamous cell carcinoma of the skin. Surprisingly, we show that samples of basal cell carcinoma demonstrated strong staining for TG3 both in the cytoplasm and nucleus. Furthermore, at the mRNA level, the expression pattern of TGM3 was crucially altered in BCC, but not other types of skin cancer. Conclusion: These findings lead to new questions regarding TG3 involvement in basal cell carcinoma tumourigenesis. Moreover, the expression pattern of TG3 renders it a potential specific marker for basal cell carcinoma diagnosis.

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“…Li et al [ 31 ] demonstrated that TGM-3 can be a candidate tumour suppressor that is able to induce EC cell proliferation and migration by down regulating the NF-κB signalling pathway, indicating that TGM-3 may serve as a useful biomarker and therapeutic target for esophageal cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

Tissue and serum expression of TGM-3 may be prognostic marker in patients of oral squamous cell carcinoma undergoing chemo-radiotherapy

et al. 2018

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Radioresistance is one of the main determinants of treatment outcome in oral squamous cell carcinoma (OSCC), but its prediction is difficult. Several authors aimed to establish radioresistant OSCC cell lines to identify genes with altered expression in response to radioresistance. The development of OSCC is a multistep carcinogenic process that includes activation of several oncogenes and inactivation of tumour suppressor genes. TGM-3 is a tumour suppressor gene and contributes to carcinogenesis process. The aim of this study was to estimate serum and tissue expression of TGM-3 and its correlation with clinico-pathological factors and overall survival in patients of OSCC undergoing chemo-radiotherapy. Tissue expression was observed in formalin fixed tissue biopsies of 96 cases of OSCC and 32 healthy controls were subjected to immunohistochemistry (IHC) by using antibody against TGM-3 and serum level was estimated by ELISA method. mRNA expression was determined by using Real-Time PCR. Patients were followed for 2 year for chemo radiotherapy response. In OSCC, 76.70% cases and in controls 90.62% were positive for TGM-3 IHC expression. TGM-3 expression was cytoplasmic and nuclear staining expressed in keratinized layer, stratum granulosum and stratum spinosum in controls and tumour cells. Mean serum TGM-3 in pre chemo-radiotherapy OSCC cases were 1304.83±573.55, post chemo-radiotherapy samples were 1530.64±669.33 and controls were 1869.16±1377.36, but difference was significant in pre chemo-radiotherapy samples as compared to controls (p<0.018). This finding was also confirmed by real- time PCR analysis in which down regulation (-7.92 fold change) of TGM-3 in OSCC as compared to controls. TGM-3 expression was significantly associated with response to chemo-radiotherapy treatment (p<0.007) and overall survival (p<0.015). Patents having higher level of TGM-3 expression have good response to chemo-radiotherapy and also have better overall survival. TGM-3 may serve as a candidate biomarker for responsiveness to chemo-radiotherapy treatment in OSCC patients.

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Transglutaminase 3 protein modulates human esophageal cancer cell growth by targeting the NF-κB signaling pathway

Cited by 20 publications

References 43 publications

Significantly mutated genes and regulatory pathways in SCLC—a meta-analysis

Significantly mutated genes and regulatory pathways in SCLC—a meta-analysis

Transglutaminase 3 is expressed in basal cell carcinoma of the skin

Tissue and serum expression of TGM-3 may be prognostic marker in patients of oral squamous cell carcinoma undergoing chemo-radiotherapy

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