Keratin forms the major intermediate filament network in several epithelial cell types, including carcinomas. The German collaborators now find that in cancer cell lines these networks are sensitive to sphingosylphosphorylcholine (SPC), a blood plasma lipid that is elevated in certain metastases. SPC is thus the first physiological compound shown to alter keratin organization. SPC treatment of pancreatic and gastric cancer cells reduced cytoplasmic keratin filaments, which relocated to form a ring of newly phosphorylated filaments surrounding the nucleus.
The group found that the keratin filaments were the main determinant of cellular elasticity. The SPC-induced rearrangement made the cells more flexible and also allowed migration— a dangerous combination for tumor cells. “The first step in metastasis is to get into the bloodstream,” says Seufferlein. “This could be facilitated by compounds like SPC. Then the cells can change shape and squeeze through [tight] areas.” Primary cells still need to be examined to determine whether keratin in noncancerous cells responds similarly to SPC. ▪