The regulation and role of osteopontin in malignant transformation and cancer.
Osteopontin (OPN) is a predominantly secreted extracellular matrix glycophosphoprotein which binds to alpha v-containing integrins and has an important role in malignant cell attachment and invasion. High OPN expression in the primary tumor is associated with early metastasis and poor outcome in human breast and other cancers. Forced OPN overexpression in benign cells may induce neoplastic-like cell behaviour including increased attachment and invasion in vitro as well as the ability to metastasize in vivo. Conversely, OPN inhibition by antisense cDNA impedes cell growth and tumor forming capacity. OPN is not mutationally activated in cancer but its expression is regulated by Wnt/Tcf signaling, steroid receptors, growth factors, ras, Ets and AP-1 transcription factors. Presumably these factors are implicated in induction of OPN overexpression in cancer. Greater understanding of the role of OPN in neoplastic change and its transcriptional regulation may enable development of novel cancer treatment strategies.
El-Tanani
Mohamed K
MK
Centre for Cancer Research and Cell Biology, Queen's University Belfast, University Floor, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, United Kingdom. m.el-tanani@qub.ac.uk
Campbell
Frederick Charles
FC
Kurisetty
Vittal
V
Jin
Dachuan
D
McCann
Mella
M
Rudland
Philip S
PS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D017124:Conserved Sequence; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D053495:Osteopontin / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D004273:DNA, Neoplasm; D053495:Osteopontin