The cleavage of semaphorin 3C induced by ADAMTS1 promotes cell migration.
Metastasis is a sequential process that allows cells to move from the primary tumor and grow elsewhere. Because of their ability to cleave a variety of extracellular signaling and adhesion molecules, metalloproteases have been long considered key components of the metastatic program. However, the function of certain metalloproteases, such as ADAMTS1, is not clear and seems to depend on the cellular environment and/or the stage of tumor progression. To characterize the function of ADAMTS1, we performed two alternative proteomic approaches, difference gel electrophoresis and stable isotope labeling by amino acids in cell culture, to identify novel substrates of the metalloprotease. Both techniques showed that overexpression of ADAMTS1 leads to the release of semaphorin 3C from the extracellular matrix. Although semaphorins are well known regulators of axon guidance, accumulating evidence shows that they may also participate in tumor progression. Here, we show that the cleavage of semaphorin 3C induced by ADAMTS1 promotes the migration of breast cancer cells, indicating that the co-expression of these molecules in tumors may contribute to the metastatic program.
Esselens
Cary
C
Medical Oncology Research Program, Research Institute Foundation and Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Psg. Vall d'Hebron 119-129, 08035 Barcelona, Spain.
Malapeira
Jordi
J
Colomé
Núria
N
Casal
Carmen
C
Rodríguez-Manzaneque
Juan Carlos
JC
Canals
Francesc
F
Arribas
Joaquín
J
D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000071097:ADAMTS1 Protein; D001943:Breast Neoplasms / Q000378:metabolism* / Q000556:secondary*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D040901:Proteomics; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D014162:Transfection; D014471:Umbilical Veins / Q000166:cytology
C543908:Sema3C protein, human; D039961:Semaphorins; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human