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We previously reported that normal fibroblasts (NFs) and, notably, breast cancer-associated fibroblasts (CAFs) induced epithelial-to-mesenchymal transition and increases in cell membrane fluidity and migration in well- (MCF-7) and poorly-differentiated (MDA-MB-231) breast cancer cells.
The CAF-triggered increase in SCD1 expression is consistent with the CAF-mediated enhancement of cancer cell membrane fluidity and migration that we have previously demonstrated (Angelucci et al, 2012).
To identify an upstream target in the control of cancer cell membrane fluidity and migration exerted notably by CAFs, we carried out Western blotting and ELISA and evaluated protein expression and DNA binding activity of the SCD1 transcription factor (SREBP1) in breast cancer cells after 6 days of co-culture with NFs or CAFs.
To shed light on the molecular basis of the previously observed increase induced by NFs and CAFs in cancer cell plasma membrane fluidity and migration (Angelucci et al, 2012), we co-cultured MCF-7 and MDA-MB-231 cells with NFs or CAFs and investigated the effect of such interaction on SCD1 gene and protein expression in cancer cells.
On the basis of the above evidence, we could reasonably assume that the fibroblast-induced upregulation of SCD1 gene and/or protein expression in tumor cells substantially contributes to the previously observed increases in both cancer cell membrane fluidity and migration triggered by CAFs (Angelucci et al, 2012).
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As already discussed above, changes in lipid desaturation mediated by altered SCD expression could affect membrane fluidity and contribute to the induction of cancer cell migration, a process that is also regulated by hypoxia.
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