An increase in integrin-linked kinase non-canonically confers NF-κB-mediated growth advantages to gastric cancer cells by activating ERK1/2

Tseng, Po Chun; Chen, Chia Ling; Shan, Yan Shen; Chang, Wen Teng; Liu, Hsiao Sheng; Hong, Tse-Ming; Hsieh, Chia Yuan; Lin, Sheng Hsiang; Lin, Chiou Feng

doi:10.1186/s12964-014-0069-3

Cited by 15 publications

(12 citation statements)

References 66 publications

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“…e, Akt stimulates IKK by phosphorylation and subsequently, IKK activates NF-κB by phosphorylating the inhibitor of κB, which may mask the nuclear localization signals of NF-κB and keep it sequestered in an inactive state in the cytoplasm. Activated NF-κB may be translocated into the nucleus where it transcriptionally upregulates multiple genes, including positive cell-cycle regulators, anti-apoptotic and pro-survival factors (14,88,96). Arrowheads and perpendicular lines indicate stimulation and inhibition of downstream substrates, respectively; straight lines and dotted lines indicate direct and indirect effects on downstream substrates, respectively.…”

Section: Pten Mediates Oncogenic Activities Of Mirnas Via Pi3k/akt Simentioning

confidence: 99%

“…In GC cells, it has been suggested that the activation of PI3K or loss of PTEN was able to protect integrin-linked kinase (ILK) from proteasome-mediated degradation (88). Enhanced ILK may subsequently activate Ras and promote the formation of the IQ motif-containing GTPase-activating protein 1-Ras complex, which stimulated the c-Raf/MEK1/2/ERK1/2/ribosomal S6 kinase/inhibitor of κBα/nuclear factor (NF)-κB signaling, leading to the increased cell growth, migration and decreased sensitivity of 5-FU and DDP (88). Consistently, miR-128b was reported to repress GC cell growth, invasion and promote apoptosis through Akt/NF-κB signaling due to its negative post-transcriptional regulation of PDK1 (89).…”

Section: Pten Mediates Oncogenic Activities Of Mirnas Via Pi3k/akt Simentioning

confidence: 99%

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MicroRNAs and the PTEN/PI3K/Akt pathway in gastric cancer (Review)

Zhu

Xiong

et al. 2019

Oncol Rep

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Gastric carcinogenesis arises from complicated interactions among host, environmental and bacterial factors, which cause genetic and epigenetic dysregulation of oncogenic and tumor-suppressive genes. MicroRNAs (miRNAs), a class of small non-coding RNAs that post-transcriptionally regulate ~30% human genes, may serve as oncogenes or tumor-suppressors in malignancies, including gastric cancer (GC). Although miRNA dysregulation commonly exists in GC, exact roles miRNAs serve in the pathogenesis and promotion of this tumor remain undetermined. Recently, results of previous studies regarding mechanisms underlying miRNAs generally converged on pathways critical in cellular processes, including cell proliferation, apoptosis and invasion, among which phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling is a fundamental one, with frequent oncogenic alterations in GC. Therefore, in the present review, the disorder and function of miRNAs and PTEN/PI3K/Akt signaling in GC are discussed. Additionally, how miRNAs transduce their effects by regulating this pathway, particularly in GC stem cells and the tumor microenvironment, and two novel hypotheses significant in carcinogenesis, tumor progression and recurrence, are discussed. Furthermore, the roles of miRNAs and the PTEN/PI3K/Akt pathway in target therapies against this lethal disease are outlined.

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Section: Pten Mediates Oncogenic Activities Of Mirnas Via Pi3k/akt Simentioning

confidence: 99%

Section: Pten Mediates Oncogenic Activities Of Mirnas Via Pi3k/akt Simentioning

confidence: 99%

MicroRNAs and the PTEN/PI3K/Akt pathway in gastric cancer (Review)

Zhu

Xiong

et al. 2019

Oncol Rep

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“…ILK facilitates the formation of the IQ motif-containing GTPase-activating protein 1 (IQGAP1)-Ras complex leading to activation of Ras/c-Raf/MEK1/2/ERK1/2, ribosomal S6 kinase and NF-κB signaling in AGS, SNU-1, MKN45, GES-1 gastric cancer cell lines. This signaling promoted cell growth, migration and reduced the sensitivity of gastric cancer cells to the anticancer agents 5-fluorouracil and cisplatin [ 105 ].…”

Section: Tumor-promoting Effectors and Nf-κb Regulation In Gastricmentioning

confidence: 99%

NF‐κB Signaling in Gastric Cancer

Sokolova

Naumann

2017

Toxins

175

122

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Gastric cancer is a leading cause of cancer death worldwide. Diet, obesity, smoking and chronic infections, especially with Helicobacter pylori, contribute to stomach cancer development. H. pylori possesses a variety of virulence factors including encoded factors from the cytotoxin-associated gene pathogenicity island (cagPAI) or vacuolating cytotoxin A (VacA). Most of the cagPAI-encoded products form a type 4 secretion system (T4SS), a pilus-like macromolecular transporter, which translocates CagA into the cytoplasm of the host cell. Only H. pylori strains carrying the cagPAI induce the transcription factor NF-κB, but CagA and VacA are dispensable for direct NF-κB activation. NF-κB-driven gene products include cytokines/chemokines, growth factors, anti-apoptotic factors, angiogenesis regulators and metalloproteinases. Many of the genes transcribed by NF-κB promote gastric carcinogenesis. Since it has been shown that chemotherapy-caused cellular stress could elicit activation of the survival factor NF-κB, which leads to acquisition of chemoresistance, the NF-κB system is recommended for therapeutic targeting. Research is motivated for further search of predisposing conditions, diagnostic markers and efficient drugs to improve significantly the overall survival of patients. In this review, we provide an overview about mechanisms and consequences of NF-κB activation in gastric mucosa in order to understand the role of NF-κB in gastric carcinogenesis.

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“…ILK, a highly conserved, 59 kDa serine/threonine kinase, has been involved in controlling various biological processes that are crucial to the progression of malignant disease [16]. ILK promotes tumor proliferation and cell-cycle progression in many types of cancer, but its function in osteosarcoma is less clear [24,25]. In our study, the results of dual-luciferase assay revealed the targeting regulatory relations between miR-542-3p and ILK , which proved that ILK is a target of miR-542-3p.…”

Section: Discussionmentioning

confidence: 99%

MicroR-542-3p can mediate ILK and further inhibit cell proliferation, migration and invasion in osteosarcoma cells

Cai

Zuo

2019

Aging

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MiR-542-3p and its target gene integrin linked kinase (ILK) in human osteosarcoma together with the differentially expressed genes from osteosarcoma tissues was analyzed through bioinformatics analysis in this study. Real time quantitative polymerase chain reaction (qRT-PCR) and western blot showed that the miR-542-3p expression decreased while the ILK expression increased in the osteosarcoma tissues. The overexpressed miR-542-3p or silenced ILK restrained cell invasion, proliferation and migration and arrested cell cycle, facilitated cell apoptosis in U-2OS and 143B cells. The dual-luciferase assay confirmed the targeting relationship between miR-542-3p and ILK. MiR-542-3p overexpression inhibited osteosarcoma growth in vivo. In conclusion, miR-542-3p overexpression down-regulated its target gene ILK, promoted osteosarcoma cells apoptosis and inhibited their proliferation, migration and invasion.

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An increase in integrin-linked kinase non-canonically confers NF-κB-mediated growth advantages to gastric cancer cells by activating ERK1/2

Cited by 15 publications

References 66 publications

MicroRNAs and the PTEN/PI3K/Akt pathway in gastric cancer (Review)

MicroRNAs and the PTEN/PI3K/Akt pathway in gastric cancer (Review)

NF‐κB Signaling in Gastric Cancer

MicroR-542-3p can mediate ILK and further inhibit cell proliferation, migration and invasion in osteosarcoma cells

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