Significance of AKT in gastric cancer (Review)

Sasaki, Takuma; Kuniyasu, Hiroki

doi:10.3892/ijo.2014.2678

Cited by 49 publications

(41 citation statements)

References 28 publications

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“…Previous studies have found that the abnormal phosphorylation of AKT and ERK1/2 was associated with the proliferation, growth, angiogenesis, invasion and metastasis of gastric cancer (23,24), and was regarded as the bridge between CXCR1/2 and downstream molecules (10,25,26). Our results confirm this finding and show that CXCR1 knockdown suppressed the phosphorylation of AKT and ERK1/2.…”

Section: Discussionsupporting

confidence: 94%

CXCR1 promotes malignant behavior of gastric cancer cells in vitro and in vivo in AKT and EKR1/2 phosphorylation

Wang

et al. 2016

International Journal of Oncology

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CXCR1 is a member of the chemokine receptor family, which was reported to play an important role in several cancers. The present study investigated the influence of CXCR1 stable knockdown or overexpression on the malignant behavior of gastric cancer cells in vitro and in vivo and the potential mechanisms. MKN45 and BGC823 cells were stably transfected with plasmid pYr-1.1-CXCR1-shRNA (knockdown) and pIRES2-ZsGreen1-CXCR1 (overexpression), respectively. Malignant behavior was evaluated in vitro for changes in proliferation by MTT and colony forming assays; cell cycle and apoptosis by flow cytometry; and migration and invasion using transwell and wound-healing assays. Proliferation, cell cycle, apoptosis, migration and invasion-related signaling molecule expression were measured by real-time RT-PCR and western blot analysis. CXCR1 knockdown and overexpressing xenografts were monitored for in vivo tumor growth. Stable knockdown of CXCR1 inhibited MKN45 cell proliferation, migration and invasion, but were reversed in BGC823 cells stably overexpressing CXCR1. In addition, MKN45 cells stably transfected with CXCR1 shRNA inhibited AKT and ERK1/2 phosphorylation, protein expression of cyclin D1, EGFR, VEGF, MMP-9, MMP-2 and Bcl-2, and increased protein expression of Bax and E-cadherin (all P<0.05). In vivo CXCR1-shRNA-MKN45 cells transplanted into nude mice formed smaller tumors than non-transfected or scrambled-shRNA cells (both P<0.05). In contrast BGC823 cells overexpressing CXCR1 formed larger tumors in mice than cells carrying an empty expression plasmid or non-transfected cells (both P<0.05). CXCR1 promoted gastric cancer cell proliferation, migration and invasion. The present study provides preclinical data to support CXCR1 as a novel therapeutic target for gastric cancer.

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Section: Discussionsupporting

confidence: 94%

CXCR1 promotes malignant behavior of gastric cancer cells in vitro and in vivo in AKT and EKR1/2 phosphorylation

Wang

et al. 2016

International Journal of Oncology

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“…AKT is a primary signaling transducer of the phosphoinositide 3-kinase (PI3K) pathway and contributes to cancer progression by inhibiting apoptosis, promoting cell proliferation and regulating migration and invasion in many cancer types [21–22]. Previous studies have shown that the PI3K/AKT pathway is frequently activated in GC and revealed that PI3K/AKT signal transduction pathway participates in cell proliferation with regulators such as FOXO1, BCL-2 and BAX [23–24].…”

Section: Discussionmentioning

confidence: 99%

HOXB7 overexpression promotes cell proliferation and correlates with poor prognosis in gastric cancer patients by inducing expression of both AKT and MARKs

He¹,

Liu²,

Xia³

et al. 2016

Oncotarget

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Increased expression of HOXB7 has been reported to correlate with the progression in many cancers. However, the specific mechanism by which it promotes the evolution of gastric cancer (GC) is poorly understood.In this study, we sought to investigate the role of HOXB7 in GC by assessing HOXB7 expression in patient tissue and its correlation to clinical characteristics. We found that GC tissues showed increased expression of HOXB7 and that the HOXB7 expression was significantly associated with Lauren classification, invasion depth, lymphatic metastasis and poor prognosis, and could serve as an independent prognostic factor. To further investigate the role of HOXB7 in GC, we generated stable GC cell lines and both over-expressed and knocked down HOXB7 expression. Over-expression of HOXB7 in GC cell lines enhanced cell proliferation, colony formation, migration and invasion ability, whereas the opposite trends were observed upon reduction of HOXB7 expression by knockdown. These findings were further supported by our in vivo studies which show that HOXB7 expression can affect the GC cells' subcutaneous growth and lung metastases. A Phospho-MAPK Array Kit was used to explore the possible mechanism of HOXB7-induced cell proliferation and invasion. We found that the AKT signaling pathway and the two members of the MAPK pathway, were involved in those promoting effects. In conclusion, our results showed that increased expression of HOXB7 might play an important role in promoting GC proliferation, migration and invasion by inducing both AKT and MAPK pathways, thus resulting in progression of, and poor prognosis in GC patients.

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“…It plays important roles in diverse cell processes including differentiation, proliferation, survival, and metabolism (Sasaki and Kuniyasu, 2014). AKT has pleckstrin homology (PH) domain.…”

Section: Tgr5 and Cell Signalingmentioning

confidence: 99%

TGR5, Not Only a Metabolic Regulator

2016

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G-protein-coupled bile acid receptor, Gpbar1 (TGR5), is a member of G-protein-coupled receptor (GPCR) superfamily. High levels of TGR5 mRNA were detected in several tissues such as small intestine, stomach, liver, lung, especially in placenta and spleen. TGR5 is not only the receptor for bile acids, but also the receptor for multiple selective synthetic agonists such as 6α-ethyl-23(S)-methyl-cholic acid (6-EMCA, INT-777) and a series of 4-benzofuranyloxynicotinamde derivatives to regulate different signaling pathways such as nuclear factor κB (NF-κB), AKT, and extracellular signal-regulated kinases (ERK). TGR5, as a metabolic regulator, is involved in energy homeostasis, bile acid homeostasis, as well as glucose metabolism. More recently, our group and others have extended the functions of TGR5 to more than metabolic regulation, which include inflammatory response, cancer and liver regeneration. These findings highlight TGR5 as a potential drug target for different diseases. This review summarizes the basic information of TGR5 and its new functions.

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Significance of AKT in gastric cancer (Review)

Cited by 49 publications

References 28 publications

CXCR1 promotes malignant behavior of gastric cancer cells in vitro and in vivo in AKT and EKR1/2 phosphorylation

CXCR1 promotes malignant behavior of gastric cancer cells in vitro and in vivo in AKT and EKR1/2 phosphorylation

HOXB7 overexpression promotes cell proliferation and correlates with poor prognosis in gastric cancer patients by inducing expression of both AKT and MARKs

TGR5, Not Only a Metabolic Regulator

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