Comparison of the Regulation of β-Catenin Signaling by Type I, Type II and Type III Interferons in Hepatocellular Carcinoma Cells

Li, Wei; Huang, Xiaojie; Tong, Hongfei; Wang, Yuxuan; Zhang, Tong; Wang, Wen; Dai, Lili; Li, Tongzeng; Lin, Shigang; Wu, Hao

doi:10.1371/journal.pone.0047040

Cited by 21 publications

(18 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…STAT3 is activated through phosphorylation by a wide range of cytokines and growth factors in response to various stimuli (28)(29)(30)(31). We found that central nesfatin-1/NUCB2 knockdown suppressed phosphorylation of STAT3 at Ser727 and Tyr705 in the liver.…”

Section: Discussionmentioning

confidence: 79%

Hypothalamic Nesfatin-1/NUCB2 Knockdown Augments Hepatic Gluconeogenesis That Is Correlated With Inhibition of mTOR-STAT3 Signaling Pathway in Rats

Yang

Chen

et al. 2014

Diabetes

View full text Add to dashboard Cite

Nesfatin-1, an 82-amino acid neuropeptide, has recently been characterized as a potent metabolic regulator. However, the metabolic mechanisms and signaling steps directly associated with the action of nesfatin-1 have not been well delineated. We established a loss-of-function model of hypothalamic nesfatin-1/NUCB2 signaling in rats through an adenoviral-mediated RNA interference. With this model, we found that inhibition of central nesfatin-1/NUCB2 activity markedly increased food intake and hepatic glucose flux and decreased glucose uptake in peripheral tissue in rats fed either a normal chow diet (NCD) or a highfat diet (HFD). The change of hepatic glucose fluxes in the hypothalamic nesfatin-1/NUCB2 knockdown rats was accompanied by increased hepatic levels of glucose-6-phosphatase and PEPCK and decreased insulin receptor, insulin receptor substrate 1, and AKT kinase phosphorylation. Furthermore, knockdown of hypothalamic nesfatin-1 led to decreased phosphorylation of mammalian target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3) and the subsequent suppressor of cytokine signaling 3 levels. These results demonstrate that hypothalamic nesfatin-1/NUCB2 plays an important role in glucose homeostasis and hepatic insulin sensitivity, which is, at least in part, associated with the activation of the mTOR-STAT3 signaling pathway. Diabetes 2014;63:123463: -124763: | DOI: 10.2337 The hypothalamus, where numerous neuropeptides and transmitters are released to control essential body functions, has been considered a key integrator in the central control of food intake and energy balance (1,2). Oh-I et al. (3) discovered nesfatin-1, an 82-amino acid polypeptide, while searching for new appetite-controlling signals. Nesfatin-1 is the cleavage product of the calcium and DNA-binding protein nucleobindin2 (NUCB2),

show abstract

Section: Discussionmentioning

confidence: 79%

Hypothalamic Nesfatin-1/NUCB2 Knockdown Augments Hepatic Gluconeogenesis That Is Correlated With Inhibition of mTOR-STAT3 Signaling Pathway in Rats

Yang

Chen

et al. 2014

Diabetes

View full text Add to dashboard Cite

show abstract

“…In addition, IFNγ decreases tumor cell growth by inducing tumor cell cycle arrest, apoptosis and necroptosis. In cancer types, such as breast cancer, colorectal cancer and hepatocellular cancer, IFNγ can exert antiproliferative effect on tumor cells by enhancing expression of the cell cycle inhibitor proteins p27Kip, p16 or p21. Moreover, in colorectal cell lines, IFNγ elicits autophagy‐associated apoptosis through induction of mitochondria‐derived reactive oxygen species (ROS), which is dependent on cytosolic phospholipase A2 (cPLA2) activation .…”

Section: The Role Of Ifnγ In Immune Eliminationmentioning

confidence: 99%

Interferon gamma in cancer immunotherapy

2018

Cancer Medicine

274

181

View full text Add to dashboard Cite

Immune system can recognize self vs transformed self. That is why cancer immunotherapy achieves notable benefits in a wide variety of cancers. Recently, several papers reported that immune checkpoint blockade therapy led to upregulation of IFNγ and in turn clearance of tumor cells. In this review, we conducted an extensive literature search of recent 5‐year studies about the roles of IFNγ signaling in both tumor immune surveillance and immune evasion. In addition to well‐known functions, IFNγ signaling also induces tumor ischemia and homeostasis program, resulting in tumor clearance and tumor escape, respectively. The yin and the yang of IFNγ signaling are summarized. Thus, this review helps us to comprehensively understand the roles of IFNγ in tumor immunity, which contributes to better design and management of clinical immunotherapy approaches.

show abstract

“…It has been well documented that the β-catenin and STAT3 signaling pathways are important in the evasion of apoptosis of cancer cells (15)(16)(17)(18). The final critical stage of apoptosis is achieved through caspase activation, in which the role of caspase-3 is particularly important.…”

Section: Discussionmentioning

confidence: 99%

Simultaneous silencing of β-catenin and signal transducer and activator of transcription 3 synergistically induces apoptosis and inhibits cell proliferation in HepG2 liver cancer cells

Wang

Liu

Huang

et al. 2015

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. The tumorigenesis and maintenance of a cancer cells is dependent upon the collaboration of multiple signaling pathways. Signal transducer and activator of transcription 3 (STAT3) and β-catenin are at the center of multiple cancer-associated signaling pathways; therefore, simultaneously targeting STAT3 and β-catenin may be a potential cancer treatment, leading to induced lethality of cancer cells. In the present study, HepG 2 liver cancer cells were transfected with small interfering RNA (siRNA) against β-catenin and STAT3 alone or in combination. The cell growth was assessed using an MTT assay and the levels of cell apoptosis were detected using flow cytometry. Protein levels of caspase-3, cleaved caspase-3, poly(ADP-ribose) polymerase (PARP) and cleaved PARP were determined using western blot analysis. Following siRNA transfection, β-catenin and STAT3 protein levels decreased at 72 h. HepG 2 cell growth inhibition and early apoptosis in the β-catenin and STAT3 siRNA co-transfection group were significantly greater than those in the groups transfected with β-catenin or STAT3 siRNA alone. Decreased caspase-3 and PARP levels, as well as enhanced cleavage of caspase-3 and PARP were observed in the β-catenin and STAT3 co-transfection group. Simultaneous silencing of β-catenin and STAT3 using siRNAs resulted in an enhanced loss of cell viability and induction of apoptosis in HepG 2 liver cancer cells, suggesting that these genes are promising targets for the further preclinical and clinical development of anti-cancer therapeutic strategies, which target several cancer signaling pathways simultaneously.

show abstract

Comparison of the Regulation of β-Catenin Signaling by Type I, Type II and Type III Interferons in Hepatocellular Carcinoma Cells

Cited by 21 publications

References 32 publications

Hypothalamic Nesfatin-1/NUCB2 Knockdown Augments Hepatic Gluconeogenesis That Is Correlated With Inhibition of mTOR-STAT3 Signaling Pathway in Rats

Hypothalamic Nesfatin-1/NUCB2 Knockdown Augments Hepatic Gluconeogenesis That Is Correlated With Inhibition of mTOR-STAT3 Signaling Pathway in Rats

Interferon gamma in cancer immunotherapy

Simultaneous silencing of β-catenin and signal transducer and activator of transcription 3 synergistically induces apoptosis and inhibits cell proliferation in HepG2 liver cancer cells

Contact Info

Product

Resources

About