Maspin alters the carcinoma proteome.
Maspin, a member of the serine protease inhibitor (serpin) family, is a tumor suppressor in breast and prostate cancer. To address molecular mechanisms underlying maspin's activity, we restored its expression in invasive carcinoma cells and analyzed the resulting changes by shotgun proteomics. Using a mass spectrometry-based multidimensional proteomic method, we observed changes to the expression of approximately 27% of the detectable proteome. In particular, we noted changes to the expression of proteins that regulate cytoskeletal architecture, cell death, and protein turnover. In each case, changes in protein expression were accompanied by measurable changes in tumor cell phenotype. Thus, maspin-expressing cells exhibit a more prominent actin cytoskeleton, a reduced invasive capacity, an increased rate of spontaneous apoptosis, and an altered proteasome function. These observations reveal for the first time the far reaching effects of maspin on multiple protein networks and a new hypothesis of maspin function based on the regulation of proteasome function.
Chen
Emily I
EI
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA. emilyc@scripps.edu
Florens
Laurence
L
Axelrod
Fumiko T
FT
Monosov
Edward
E
Barbas
Carlos F
CF
Yates
John R
JR
Felding-Habermann
Brunhilde
B
Smith
Jeffrey W
JW
D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000517:prevention & control; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D020543:Proteome; D015843:Serpins / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism
D020543:Proteome; C085344:SERPIN-B5; D015843:Serpins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex