Abstract
An aberrant expression of integrin β1 has been implicated in breast cancer progression. Here, we compared the cell behaviors of wild-type (WT), β1 gene deleted (KO), and β1 gene restored (Res) MDA-MB-231 cells. Surprisingly, the expression of β1 exhibited opposite effects on cell proliferation. These effects were dependent on cell densities, and they showed an up-regulation of cell proliferation when cells were cultured under sparse conditions, and a down-regulation of cell growth under dense conditions. By comparison with WT cells, the phosphorylation levels of ERK in KO cells were consistently suppressed under sparse culture conditions, but consistently up-regulated under dense culture conditions. The phosphorylation levels of EGFR were increased in the KO cells. By contrast, the phosphorylation levels of AKT were decreased in the KO cells. The abilities for both colony and tumor formation were significantly suppressed in the KO cells, suggesting that β1 plays an important role in cell survival signaling for tumorigenesis. These aberrant phenotypes in the KO cells were rescued in the Res cells. Taken together, these results clearly showed the distinct roles of β1 in cancer cells: the inhibition of cell growth and the promotion of cell survival, which may shed light on cancer therapies.
Highlights
An aberrant expression of integrin β1 has been implicated in breast cancer progression
Integrins comprise a group of transmembrane heterodimeric proteins consisting of α and β subunits[1] that drive most of the interactions between cells and the extracellular matrix (ECM). β 1 integrin, which constitutes the largest subgroup of integrins, is aberrantly expressed in human breast carcinoma and contributes to diverse malignant phenotypes, including epithelial-to-mesenchymal transition (EMT), metastasis, and angiogenesis[2,3,4]
Here we investigated the biological functions of β 1 in wild-type (WT) cells, the deletion of the β 1 gene (KO), and the restoration of the β 1 gene in KO (Res) MDA-MB-231 cells, and found that β 1 exhibited opposite effects on cell proliferation that were dependent on cell densities: up-regulation of cell proliferation when cells were cultured under sparse conditions, and down-regulation of cell growth when cells were cultured under dense conditions
Summary
An aberrant expression of integrin β1 has been implicated in breast cancer progression. The phosphorylation levels of AKT were decreased in the KO cells The abilities for both colony and tumor formation were significantly suppressed in the KO cells, suggesting that β1 plays an important role in cell survival signaling for tumorigenesis. The roles of β 1 in these processes remain unclear To solve these issues, here we investigated the biological functions of β 1 in wild-type (WT) cells, the deletion of the β 1 gene (KO), and the restoration of the β 1 gene in KO (Res) MDA-MB-231 cells, and found that β 1 exhibited opposite effects on cell proliferation that were dependent on cell densities: up-regulation of cell proliferation when cells were cultured under sparse conditions, and down-regulation of cell growth when cells were cultured under dense conditions. Our study clearly showed the dynamic regulation by β 1 for cell behavior, which may provide an underlying mechanism for the possibility of drug resistance due to β 1 presence, and highlights the importance of combination treatment including β 1 integrin and EGFR
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