Hypoxia-inducible factor-1α and Wnt/β-catenin signaling pathways promote the invasion of hypoxic gastric cancer cells

Liu, Hong‐Lan; Liu, Dang; Ding, Guang-Rong; Liao, Pengfei; Jun-wen, Zhang

doi:10.3892/mmr.2015.3812

Cited by 41 publications

(36 citation statements)

References 25 publications

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“…Surprisingly, hypoxia (24 hours) did not affect invasiveness although previous studies have shown hypoxia to promote the invasiveness of human PCa cells [eg 45,46 ]. Indeed, the effect of hypoxia in promoting cellular invasiveness has been reported also for other cancers, for example colon, 34 breast 47,48 and gastric cancer 49 . The apparent lack of effect in the present study could be due to the “normoxic” Mat‐LyLu cells also having some properties usually associated with hypoxia.…”

Section: Discussioncontrasting

confidence: 71%

Riluzole: Anti‐invasive effects on rat prostate cancer cells under normoxic and hypoxic conditions

Rizaner

Uzun

Fraser

et al. 2020

Basic Clin Pharma Tox

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Anti‐invasive effects of riluzole and ranolazine, a neuro‐protectant and an anti‐anginal drug, respectively, on Mat‐LyLu rat prostate cancer (PCa) cells were tested in vitro (a) at non‐toxic doses and (b) under both normoxic and hypoxic conditions, the latter common to growing tumours. Tetrodotoxin (TTX) was used as a positive control. Hypoxia had no effect on cell viability but reduced growth at 48 hours. Riluzole (5 μmol/L) or ranolazine (20 μmol/L) had no effect on cell viability or growth under normoxia or hypoxia over 24 hours. Matrigel invasion was not affected by hypoxia but inhibited by TTX, ranolazine and riluzole under a range of conditions. The expression of Nav1.7 mRNA, the prevailing, pro‐invasive voltage‐gated sodium channel α‐subunit (VGSCα), was up‐regulated by hypoxia. Riluzole had no effect on Nav1.7 mRNA expression in normoxia but significantly reduced it in hypoxia. VGSCα protein expression in plasma membrane was reduced in hypoxia; riluzole increased it but only under hypoxia. It was concluded (a) that riluzole and ranolazine have anti‐invasive effects on rat PCa cells and (b) that Nav1.7 mRNA and protein expression can be modulated by riluzole under hypoxia. Overall, therefore, riluzole and ranolazine may ultimately be “repurposed” as anti‐metastatic drugs against PCa.

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Section: Discussioncontrasting

confidence: 71%

Riluzole: Anti‐invasive effects on rat prostate cancer cells under normoxic and hypoxic conditions

Rizaner

Uzun

Fraser

et al. 2020

Basic Clin Pharma Tox

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“…We asked the question whether the extremely low levels of uPA/ uPAR as determined in rd10 mice might depend on retinal expression of HIF-1. In models of ocular pathologies characterized by HIF-1 up-regulation, uPAR is overexpressed in response to ischaemic conditions 15 suggesting a causal relationship with HIF-1 accumulation also in line with the finding that in tumour angiogenesis, HIF-1 mediates the transcription of uPA/uPAR genes during hypoxia 36,37 In this respect, mouse models of retinal degeneration as the This study also provides evidence that systemic administration of UPARANT may be an effective, non-invasive approach to alleviate the pathological signs of RP.…”

Section: Hif-1 Regulation Of Upa/upar Expressionsupporting

confidence: 54%

The urokinase‐type plasminogen activator system as drug target in retinitis pigmentosa: New pre‐clinical evidence in the rd10 mouse model

Cammalleri

Monte

Locri

et al. 2019

J Cellular Molecular Medi

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Retinitis pigmentosa (RP) is characterized by progressive loss of vision due to photoreceptor degeneration leading to secondary inflammation. The urokinase‐type plasminogen activator (uPA) system contributes to retinal inflammation, but its role in RP is unknown. In the rd10 mouse model of RP, we addressed this question with the use of the peptide UPARANT designed to interact with the uPA system. UPARANT was systemically administered from post‐natal day (PD) 10 to PD30 when its efficacy in RP rescue was investigated using electroretinographic recordings, Western blot and immunocytochemistry. Temporal profile of protein expression in the uPA system was also investigated. UPARANT reduced both Müller cell gliosis and up‐regulated levels of inflammatory markers and exerted major anti‐apoptotic effects without influencing the autophagy cascade. Rescue from retinal cell degeneration was accompanied by improved retinal function. No scotopic phototransduction was rescued in the UPARANT‐treated animals as determined by the kinetic analysis of rod‐mediated a‐waves and confirmed by rod photoreceptor markers. In contrast, the cone photopic b‐wave was recovered and its rescue was confirmed in the whole mounts using cone arrestin antibody. Investigation of the uPA system regulation over RP progression revealed extremely low levels of uPA and its receptor uPAR both of which were recovered by HIF‐1α stabilization indicating that HIF‐1 regulates the expression of the uPA/uPAR gene in the retina. Ameliorative effects of UPARANT were likely to occur through an inhibitory action on up‐regulated activity of the αvβ3 integrin/Rac1 pathway that was suggested as a novel target for the development of therapeutic approaches against RP.

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“…Certain studies have suggested that HIF-1α activation regulates the Wnt/β-catenin signaling pathway, which activates the expression of target genes and contributes to the enhanced invasion of hypoxic gastric cancer cells (35)(36)(37). CD44 is a target gene of the Wnt/β-catenin signaling pathway (38); therefore, the mechanism by which HIF-1α regulates CD44 may be associated with the Wnt/β-catenin signaling pathway in gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia regulates CD44 expression via hypoxia-inducible factor-1α in human gastric cancer cells

Liang

et al. 2016

Oncology Letters

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Abstract. Hypoxia induces proliferation and invasion in cancer cells via hypoxia-inducible factor (HIF)-1α. The cell adhesion molecule cluster of differentiation (CD) 44 has been associated with increased cell invasion and metastasis. Whether hypoxia regulates the expression of CD44 in gastric cancer cells remains to be established. In the current study, the effects of hypoxia on HIF-1α and CD44 expression levels in human gastric cell lines SGC-7901 and BGC-823 were evaluated. The cells were cultured in 1% O 2 for 1 week and then treated with 20 nM rapamycin for 72 h. Cell viability was evaluated using the Cell Counting kit-8 assay, and cell invasion was detected by the Transwell invasion assay. The protein and messenger (m) RNA expression levels of HIF-1α and CD44 were detected using western blotting and reverse transcription-quantitative polymerase chain reaction, respectively. The results revealed that cell viability and invasion increased under hypoxic conditions, but decreased following rapamycin treatment in SGC-7901 and BGC-823 cells. Hypoxia also increased the protein and mRNA expression levels of HIF-1α and CD44 in these two cell lines. However, this hypoxia-induced increase in HIF-1α and CD44 protein and mRNA expression levels was inhibited by rapamycin. These findings suggest that hypoxia induced the proliferation and invasion of SGC-7901 and BGC-823 cells. Furthermore, CD44 expression levels were potentially associated with HIF-1α expression levels. Therefore, in gastric cancer cells, hypoxia may regulate CD44 expression via HIF-1α in order to promote cell proliferation and invasion.

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Hypoxia-inducible factor-1α and Wnt/β-catenin signaling pathways promote the invasion of hypoxic gastric cancer cells

Cited by 41 publications

References 25 publications

Riluzole: Anti‐invasive effects on rat prostate cancer cells under normoxic and hypoxic conditions

Riluzole: Anti‐invasive effects on rat prostate cancer cells under normoxic and hypoxic conditions

The urokinase‐type plasminogen activator system as drug target in retinitis pigmentosa: New pre‐clinical evidence in the rd10 mouse model

Hypoxia regulates CD44 expression via hypoxia-inducible factor-1α in human gastric cancer cells

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