Stress signaling in cancer

Murakami, Shiori; Noguchi, Takuya; Takeda, Kohsuke; Ichijo, Hidenori

doi:10.1111/j.1349-7006.2007.00551.x

Cited by 25 publications

(15 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, melanoma in epidermis contains a high level of Nox4, but metastatic melanoma in lymph nodes exhibits a decrease in the Nox4 level. Elevated ROS production by up-regulated Nox enzymes may increase a risk of cancer in early stages by causing persistent proinflammatory responses (30). At least, Nox4 does not seem to contribute to the motile activity of melanoma cells, which is related to invasiveness of tumors (see Result).…”

Section: Discussionmentioning

confidence: 99%

NADPH Oxidase 4 Contributes to Transformation Phenotype of Melanoma Cells by Regulating G2-M Cell Cycle Progression

Yamaura¹,

et al. 2009

View full text Add to dashboard Cite

Generation of reactive oxygen species (ROS) has been implicated in carcinogenic development of melanoma, but the underlying molecular mechanism has not been fully elucidated. We studied the expression and function of the superoxide-generating NADPH oxidase (Nox)4 in human melanoma cells. Nox4 was up-regulated in 13 of 20 melanoma cell lines tested. Silencing of Nox4 expression in melanoma MM-BP cells by small interfering RNAs decreased ROS production and thereby inhibited anchorage-independent cell growth and tumorigenecity in nude mice. Consistently, a general Nox inhibitor, diphenylene iodonium, and antioxidants vitamine E and pyrrolidine dithiocarbamate blocked cell proliferation of MM-BP cells. Flow cytometric analysis indicated that Nox4 small interfering RNAs and diphenylene iodonium induced G 2 -M cell cycle arrest, which was also observed with another melanoma cell line, 928mel. This was accompanied by induction of the Tyr-15 phosphorylated, inactive form of cyclin-dependent kinase 1 (a hallmark of G 2 -M checkpoint) and hyperphosphorylation of cdc25c leading to its increased binding to 14-3-3 proteins. Ectopic expression of catalase, a scavenger of ROS, also caused accumulation of cells in G 2 -M phase. Immunohistochemistry revealed that expression of Nox4 was detected in 31.0% of 13 melanoma patients samples, suggesting the association of Nox4 expression with some steps of melanoma development. The findings suggest that Nox4-generated ROS are required for transformation phenotype of melanoma cells and contribute to melanoma growth through regulation of G 2 -M cell cycle progression.

show abstract

Section: Discussionmentioning

confidence: 99%

NADPH Oxidase 4 Contributes to Transformation Phenotype of Melanoma Cells by Regulating G2-M Cell Cycle Progression

Yamaura¹,

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Indeed, recent evidence suggests that malonyl-CoA decarboxylase inhibition may be a potential novel target for cancer treatment [81]. Inhibition of FASN has been shown to induce endoplasmic reticulum stress in tumor cells [82], and a further mechanism of action may involve cooperation with endoplasmic reticulum stress inducers to enhance apoptosis [83]. In addition, ceramide accumulation following siRNA inhibition of FASN may have cytotoxic effects leading to tumor cell death in breast cancer cells (which can be rescued with inhibition of ceramide synthesis) [84].…”

Section: Mechanism Of Action Of Fasn Inhibitorsmentioning

confidence: 99%

Fatty Acid Synthase As a Potential Therapeutic Target in Cancer

et al. 2010

View full text Add to dashboard Cite

Fatty acid synthase (FASN) is a key enzyme involved in neoplastic lipogenesis. Overexpression of FASN is common in many cancers, and accumulating evidence suggests that it is a metabolic oncogene with an important role in tumor growth and survival, making it an attractive target for cancer therapy. Early small-molecule FASN inhibitors such as cerulenin, C75 and orlistat have been shown to induce apoptosis in several cancer cell lines and to induce tumor growth delay in several cancer xenograft models but their mechanism is still not well understood. These molecules suffer from pharmacological limitations and weight loss as a side effect that prevent their development as systemic drugs. Several potent inhibitors have recently been reported that may help to unravel and exploit the full potential of FASN as a target for cancer therapy in the near future. Furthermore, novel sources of FASN inhibitors, such as green tea and dietary soy, make both dietary manipulation and chemoprevention potential alternative modes of therapy in the future.

show abstract

“…Recently, it was reported that FASN inhibition induces endoplasmic reticulum stress in cancer cells, and FASN inhibitors cooperate with the endoplasmic reticulum stress inducer to enhance tumour cell death (Little et al, 2007). Considering the fact that tumour microenvironment stresses are strong inducers of the endoplasmic reticulum stress (Murakami et al, 2007), the FASN inhibitors could show selective and enhanced cytotoxicity to cancer cells under the tumour microenvironment conditions.…”

Section: Fasn and De Novo Fatty-acid Synthesis As Promising Targets Omentioning

confidence: 99%

De novo fatty-acid synthesis and related pathways as molecular targets for cancer therapy

2009

View full text Add to dashboard Cite

show abstract

Stress signaling in cancer

Cited by 25 publications

References 66 publications

NADPH Oxidase 4 Contributes to Transformation Phenotype of Melanoma Cells by Regulating G2-M Cell Cycle Progression

NADPH Oxidase 4 Contributes to Transformation Phenotype of Melanoma Cells by Regulating G2-M Cell Cycle Progression

Fatty Acid Synthase As a Potential Therapeutic Target in Cancer

De novo fatty-acid synthesis and related pathways as molecular targets for cancer therapy

Contact Info

Product

Resources

About