CD24-dependent MAPK pathway activation is required for colorectal cancer cell proliferation.
CD24 is a glycosylphosphatidylinositol-anchored membrane protein reported to be overexpressed in human tumorigenesis and progression. Our purpose was to determine the role of CD24 in the proliferation of colorectal cancer cells and the potential mechanisms in this process. Our data showed that CD24 promoted cell growth and induced activation of extracellular signal-regulated kinases, Raf-1, and p38 mitogen-activated protein kinase. Furthermore, suppression of extracellular signal-regulated kinases and p38 mitogen-activated protein kinase activity by their specific inhibitors, U0126 and SB203580, abrogated CD24-induced proliferation in vitro. By tumorigenicity assay in female BALB/c nude mice, we further demonstrated that CD24 promoted tumor growth in vivo. Immunohistochemical analysis revealed that CD24 expression occurred in 92.5% of human colorectal cancer tissue, and increased with tumor progression. More importantly, the stainings of phospho-extracellular signal-regulated kinases and phospho-p38 mitogen-activated protein kinase were strongly correlated with CD24 expression. Taken together, our data suggest that CD24-dependent extracellular signal-regulated kinases and p38 mitogen-activated protein kinase activations are required for colorectal cancer cell proliferation in vitro and in vivo. The linkage of CD24 and the mitogen-activated protein kinase pathway may unravel a novel mechanism in the regulation of colorectal cancer proliferation.
Wang
Weifei
W
Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Wang
Xinying
X
Peng
Liang
L
Deng
Qiliang
Q
Liang
Yan
Y
Qing
Haitao
H
Jiang
Bo
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D051927:CD24 Antigen / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000473:pathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D019908:Proto-Oncogene Proteins c-raf / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
D051927:CD24 Antigen; C497889:CD24 protein, human; D019908:Proto-Oncogene Proteins c-raf; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases