The metastasis-associated gene CD24 is regulated by Ral GTPase and is a mediator of cell proliferation and survival in human cancer.
Ral GTPases are important mediators of transformation, tumorigenesis, and cancer progression. We recently identified the metastasis-associated protein CD24, a glycosyl phosphatidyl inositol-linked surface protein, as a downstream target of Ral signaling by profiling the expression of RalA/B-depleted bladder carcinoma cells. Because CD24 is highly expressed in bladder and many other tumor types, we sought to determine if this protein plays an essential role in maintaining the malignant phenotype. Here, we show that loss of CD24 function in cell lines derived from common tumor types is associated with decreased rates of cell proliferation, clonogenicity in soft agar, changes in the actin cytoskeleton, and induction of apoptosis. Given these phenotypes, we evaluated a human bladder cancer tissue microarray by immunohistochemistry for CD24 to determine if CD24 is a prognostic cancer biomarker. Multivariate analysis showed that increased CD24 expression correlated with shorter patient disease-free survival (P = 0.07). In conclusion, we show that CD24 is a novel and functionally relevant Ral-regulated target and a potentially important prognostic marker. We suggest that these insights may lead to future therapeutic approaches that seek to eliminate CD24 function in cancer cells.
Department of Molecular Physiology, University of Virginia, Charlottesville, Virginia, USA.
Steven C
SC
Smith
Gary
G
Oxford
Zhong
Z
Wu
Matthew D
MD
Nitz
Mark
M
Conaway
Henry F
HF
Frierson
Garret
G
Hampton
Dan
D
Theodorescu
D051927:CD24 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D048708:Cell Growth Processes / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D020725:ral GTP-Binding Proteins / Q000172:deficiency / Q000378:metabolism*
D051927:CD24 Antigen; C497889:CD24 protein, human; D034741:RNA, Small Interfering; D020725:ral GTP-Binding Proteins