CD133 suppresses neuroblastoma cell differentiation via signal pathway modification

被引：0
作者：
H Takenobu
O Shimozato
T Nakamura
H Ochiai
Y Yamaguchi
M Ohira
A Nakagawara
T Kamijo
机构：
[1] Division of Biochemistry and Molecular Carcinogenesis,Department of Pediatrics
[2] Chiba Cancer Center Research Institute,Division of Biochemistry and Innovative Cancer Therapeutics
[3] Laboratory of Anti-tumor Research,undefined
[4] Chiba Cancer Center Research Institute,undefined
[5] Core Facility for Therapeutic Vectors,undefined
[6] The Institute of Medical Science,undefined
[7] The University of Tokyo,undefined
[8] Graduate School of Medicine,undefined
[9] Chiba University,undefined
[10] Laboratory of Cancer Genomics,undefined
[11] Chiba Cancer Center Research Institute,undefined
[12] Chiba Cancer Center Research Institute,undefined
来源：
Oncogene | 2011年 / 30卷
关键词：
CD133; neuroblastoma; differentiation; RET; p38MAPK; PI3K/Akt;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
CD133 (prominin-1) is a transmembrane glycoprotein expressed on the surface of normal and cancer stem cells (tumor-initiating cells), progenitor cells, rod photoreceptor cells and a variety of epithelial cells. Although CD133 is widely used as a marker of various somatic and putative cancer stem cells, its contribution to the fundamental properties of cancer cells, such as tumorigenesis and differentiation, remains to be elucidated. In the present report, we found that CD133 was expressed in several neuroblastoma (NB) cell lines/tumor samples. Intriguingly, CD133 repressed NB cell differentiation, for example neurite extension and the expression of differentiation marker proteins, and was decreased by several differentiation stimuli, but accelerated cell proliferation, anchorage-independent colony formation and in vivo tumor formation of NB cells. NB cell line and primary tumor-sphere experiments indicated that the molecular mechanism of CD133-related differentiation suppression in NB was in part dependent on neurotrophic receptor RET tyrosine kinase regulation. RET transcription was suppressed by CD133 in NB cells and glial cell line-derived neurotrophic factor treatment failed to induce RET in CD133-expressing cells; RET overexpression rescued CD133-related inhibition of neurite elongation. Of note, CD133-related NB cell differentiation and RET repression were mainly dependent on p38MAPK and PI3K/Akt pathways. Furthermore, CD133 has a function in growth and RET expression in NB cell line- and primary tumor cell-derived tumor spheres. To the best of our knowledge, this is the first report of the function of CD133 in cancer cells and our findings may be applied to improve differentiation induction therapy for NB patients.
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页码：97 / 105
页数：8
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