TY - JOUR
T1 - Ras-transformation reduce FAM20C expression and osteopontin phosphorylation
AU - Schytte, Gitte Nørregaard
AU - Christensen, Brian Søndergaard
AU - Bregenov, Ida
AU - Sørensen, Esben Skipper
PY - 2020/9
Y1 - 2020/9
N2 - Family with sequence similarity 20, member C (FAM20C) is the main kinase of secreted phosphoproteins, including themultifunctional protein and cytokine, osteopontin (OPN). The phosphorylation of OPN varies greatly among cell types, tissues and species, and the different phospho-isoforms contribute to the multifunctionality of the protein. Expression of OPN is increased in human malignancies, and less phosphorylated isoforms of the protein have been associated with this phenotype. Here, we compared OPN from ras-transformed fibroblasts with that from their non-transformed parental cells, and found that OPN was less phosphorylated after ras-transformation. Furthermore, we demonstrated that expression of FAM20C mRNA was reduced five-fold in ras-transformed fibroblasts compared with non-transformed fibroblasts. Transfection with FAM20C of the ras-transformed fibroblasts restored the FAM20C mRNA expression but the phosphorylation of OPN was not increased proportionally. Likewise, the mRNA level of FAM20C was reduced in the malignant ras-transformed mammary cell line MCF10ACA1a compared with its non-transformed parental cell line MCF10A. These results suggest that expression of the FAM20C kinase is reduced after oncogenic ras-transformation, which potentially affects the phosphorylation of secreted phosphoproteins.
AB - Family with sequence similarity 20, member C (FAM20C) is the main kinase of secreted phosphoproteins, including themultifunctional protein and cytokine, osteopontin (OPN). The phosphorylation of OPN varies greatly among cell types, tissues and species, and the different phospho-isoforms contribute to the multifunctionality of the protein. Expression of OPN is increased in human malignancies, and less phosphorylated isoforms of the protein have been associated with this phenotype. Here, we compared OPN from ras-transformed fibroblasts with that from their non-transformed parental cells, and found that OPN was less phosphorylated after ras-transformation. Furthermore, we demonstrated that expression of FAM20C mRNA was reduced five-fold in ras-transformed fibroblasts compared with non-transformed fibroblasts. Transfection with FAM20C of the ras-transformed fibroblasts restored the FAM20C mRNA expression but the phosphorylation of OPN was not increased proportionally. Likewise, the mRNA level of FAM20C was reduced in the malignant ras-transformed mammary cell line MCF10ACA1a compared with its non-transformed parental cell line MCF10A. These results suggest that expression of the FAM20C kinase is reduced after oncogenic ras-transformation, which potentially affects the phosphorylation of secreted phosphoproteins.
UR - http://www.scopus.com/inward/record.url?scp=85091191293&partnerID=8YFLogxK
U2 - 10.1042/BSR20194378
DO - 10.1042/BSR20194378
M3 - Journal article
C2 - 32830861
SN - 0144-8463
VL - 40
JO - Bioscience Reports
JF - Bioscience Reports
IS - 9
M1 - BSR20194378
ER -