Non Animal Testing Database

Signaling mechanisms of disrupted lumen formation in breast cancer cells

Beckman Research Institute of City of Hope, Duarte, USA
The lumen formation of breast cancer cells can be restored by recovering CEACAM1 expression. SASH1 was identified as one of the top up-regulated genes during lumen restoration and was found to be critical in lumen formation. Here, human breast cancer cells transfected with CEACAM1 were grown in 3D cultures to assess the signalling mechanisms of SASH1-dependent lumen formation. The results showed that in cells with interference RNA for SASH1, DLK1 was similarly downregulated as SASH1. Additionally, the inhibition of DLK1 in CEACAM1-expressing breast cancer cells also disrupted the lumenogenesis. Furthermore, DLK1 inhibited NOTCH1 signalling and, when using other NOTCH inhibitors, lumen formation was also hindered. Overall, the researchers demonstrate that lumen formation dependent on CEACAM1 is regulated through the NOTCH1 signalling pathway and points to NOTCH1 as a potential target that acts as a tumor-promoter through its dysregulation in cancer.
The adaptor SASH1 acts through NOTCH1 and its inhibitor DLK1 in a 3D model of lumenogenesis involving CEACAM1
John E Shively
Added on: 10-31-2021
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