Ataxia-Telangiectasia, Mutated (ATM)/Nuclear Factor κ Light Chain Enhancer of Activated B Cells (NFκB) Signaling Controls Basal and DNA Damage-induced Transglutaminase 2 Expression

Ai, Lingbao; Skehan, Ryan R.; Saydi, John; Lin, Tong; Brown, Kevin D.

doi:10.1074/jbc.m112.339317

Cited by 32 publications

(33 citation statements)

References 57 publications

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“…Notably, TGM2 expression levels significantly decreased in all cell lines. Although the physiological function of TGM2 is not yet fully understood (Lorand and Graham, 2003), we hypothesized its direct role in the regulation of DNA damage response, in agreement with Ai et al (). In particular, our data highlight that radiation followed by cisplatin consistently affected DNA break‐sensing molecules such as DNA‐PK, PARP, ATM, and TGM2, as shown by their decreased expression in all the cell lines used.…”

Section: Discussionsupporting

confidence: 90%

Efficacy of Different Sequences of Radio‐ and Chemotherapy in Experimental Models of Human Melanoma

Arienti

Zoli

Pignatta

et al. 2014

Journal Cellular Physiology

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Although combination chemotherapy and radiotherapy have become the standard of care in numerous tumors, the mechanisms of interaction are often still unclear. The purpose of this study was to analyze the efficacy of radiation treatment and cisplatin sequences and to investigate their mechanisms of interaction. Three melanoma cell lines were used to evaluate in vitro radiation-induced cytotoxicity before and after cisplatin treatment. Expression levels of a panel of genes were determined by real-time RT-PCR. Cytotoxic effect was evaluated by flow cytometry analysis and Comet assay. We also used normal human dermal fibroblasts (HUDE) to evaluate the cytotoxicity of the two treatments by clonogenic assay. Radiation and cisplatin used singly were not particularly effective in reducing proliferation in melanoma cells. Conversely, radiation treatment followed by cisplatin showed a strong synergistic interaction in all cell lines, with a ratio index ranging from 16 to >100. The synergistic effect was accompanied by apoptosis induction (up to 40%) and an increase in the percentage of comet-shaped nucleoids from 85% to 99%. In parallel, our results also showed that radiation treatment of HUDE fibroblasts followed by cisplatin only induced weak cytotoxicity. Our findings highlight the efficacy of the sequence radiation → cisplatin in reducing cell proliferation and in inducing apoptosis in melanoma cell lines. This sequence also modulated a network of proteins involved in DNA damage repair.

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Section: Discussionsupporting

confidence: 90%

Efficacy of Different Sequences of Radio‐ and Chemotherapy in Experimental Models of Human Melanoma

Arienti

Zoli

Pignatta

et al. 2014

Journal Cellular Physiology

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“…This TG2 interaction with NFkB is also observed in ovarian cancer cells [34]. In addition, a TG2/NFkB positive feedback loop maintains TG2 expression and constitutive NFkB activation [46,48,49]. Phosphorylation of the Ser-216 site on TG2 appears to be required for TG2 activation of NFkB and Akt signaling and downregulation of PTEN (phosphatase and tensin homology, an inhibitor of Akt activity) [50].…”

Section: Tg2 In Breast Cancermentioning

confidence: 85%

Transglutaminase is a tumor cell and cancer stem cell survival factor

Eckert

Fisher

Grun

et al. 2015

Molecular Carcinogenesis

122

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Recent studies indicate that cancer cells express elevated levels of type II transglutaminase (TG2), and that expression is further highly enriched in cancer stem cells derived from these cancers. Moreover, elevated TG2 expression is associated with enhanced cancer stem cell marker expression, survival signaling, proliferation, migration, invasion, integrin-mediated adhesion, epithelial–mesenchymal transition, and drug resistance. TG2 expression is also associated with formation of aggressive and metastatic tumors that are resistant to conventional therapeutic intervention. This review summarizes the role of TG2 as a cancer cell survival factor in a range of tumor types, and as a target for preventive and therapeutic intervention. The literature supports the idea that TG2, in the closed/GTP-binding/signaling conformation, drives cancer cell and cancer stem cell survival, and that TG2, in the open/crosslinking conformation, is associated with cell death.

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“…For example, treatment with vorinostat, a clinically approved HDAC inhibitor, selects resistant cells that express elevated TG2, and co‐treatment of with TG2 inhibitor restores vorinostat sensitivity . TG2 knockdown also restores breast cancer cell sensitivity to doxorubicin . Thus, TG2 has emerged as an important breast cancer drug‐resistance factor.…”

Section: Tg2 In Tumor Typesmentioning

confidence: 99%

Transglutaminase 2 takes center stage as a cancer cell survival factor and therapy target

Eckert

2019

Molecular Carcinogenesis

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Transglutaminase 2 (TG2) has emerged as a key cancer cell survival factor that drives epithelial to mesenchymal transition, angiogenesis, metastasis, inflammation, drug resistance, cancer stem cell survival and stemness, and invasion and migration. TG2 can exist in a GTP‐bound signaling‐active conformation or in a transamidase‐active conformation. The GTP bound conformation of TG2 contributes to cell survival and the transamidase conformation can contribute to cell survival or death. We present evidence suggesting that TG2 has a role in human cancer, summarize what is known about the TG2 mechanism of action in a range of cancer types, and discuss TG2 as a cancer therapy target.

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Ataxia-Telangiectasia, Mutated (ATM)/Nuclear Factor κ Light Chain Enhancer of Activated B Cells (NFκB) Signaling Controls Basal and DNA Damage-induced Transglutaminase 2 Expression

Cited by 32 publications

References 57 publications

Efficacy of Different Sequences of Radio‐ and Chemotherapy in Experimental Models of Human Melanoma

Efficacy of Different Sequences of Radio‐ and Chemotherapy in Experimental Models of Human Melanoma

Transglutaminase is a tumor cell and cancer stem cell survival factor

Transglutaminase 2 takes center stage as a cancer cell survival factor and therapy target

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