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

Abstract

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.

Overexpression of CD44 Standard Isoform Upregulates HIF-1α Signaling in Hypoxic Breast Cancer Cells

“…In MDA-MB231 breast cancer cells, hypoxia-mediated HIF-1α elevation upregulated CD44 expression, and the co-localization of HRE-driven fluorescence and CD44-positive region was observed in MDA-MB-231 tumors ( Krishnamachary et al ., 2012 ). Exposure of gastric cancer cells to hypoxic conditions led to the elevation in CD44 expression ( Liang et al ., 2017 ). In the current study, we demonstrated that the overexpression of CD44s in non-aggressive breast cancer MCF-7 cells enhanced hypoxia-inducible HIF-1α accumulation, and thereby exhibited higher HRE-luciferase activity and VEGF expression during hypoxia compared to the control MCF-7.…”

Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma: Identification, Characterization and Clinical Implications

“…The interaction of HA and CD44 was found to promote epidermal growth factor receptor (EGFR)-mediated pathways in different tumor entities, in turn leading to tumor cell proliferation and survival via mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT activation [156]. Within the hypoxic tumor areas CD44 gene expression is induced via hypoxia-inducible factor (HIF)-1α [157]. In agreement with these data, increased CD44 levels were associated with tumor hypoxia in HNSCC patients [27].…”

The effect of hyaluronic acid on nucleus pulposus extracellular matrix production through hypoxia-inducible factor-1α transcriptional activation of CD44 under hypoxia

“…It has previously been shown that hypoxia potentiated the anabolic effects of HA, including the redifferentiation of articular chondrocytes and synthesis of ECM, through enhancing CD44 expression and binding affinity (Ichimaru et al, 2016). Furthermore, previous research suggested that hypoxia could enhance the expression of CD44 via HIF-1α (Liang et al, 2017). Based on the bioinformatics databases JASPAR (Web ref.…”