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Cancer Res. 2015 Oct 1;75(19):4224-34. doi: 10.1158/0008-5472.CAN-15-0412. Epub 2015 Aug 3.

Ceacam1L Modulates STAT3 Signaling to Control the Proliferation of Glioblastoma-Initiating Cells.

Author information

1
Division of Stem Cell Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan. Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
2
Laboratory for Cell Lineage Modulation, Center for Developmental Biology, RIKEN, Kobe, Hyogo, Japan.
3
Laboratory for Cell Lineage Modulation, Center for Developmental Biology, RIKEN, Kobe, Hyogo, Japan. Department of Neurosurgery, Kumamoto University Graduate School of Medical Science, Kumamoto, Kumamoto, Japan.
4
Department of Neurosurgery, Ehime University Graduate School of Medicine, To-on, Ehime, Japan.
5
Division of Stem Cell Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
6
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
7
Division of Stem Cell Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan. Laboratory for Cell Lineage Modulation, Center for Developmental Biology, RIKEN, Kobe, Hyogo, Japan. tkondo@igm.hokudai.ac.jp.

Abstract

Glioblastoma-initiating cells (GIC) are a tumorigenic cell subpopulation resistant to radiotherapy and chemotherapy, and are a likely source of recurrence. However, the basis through which GICs are maintained has yet to be elucidated in detail. We herein demonstrated that the carcinoembryonic antigen-related cell adhesion molecule Ceacam1L acts as a crucial factor in GIC maintenance and tumorigenesis by activating c-Src/STAT3 signaling. Furthermore, we showed that monomers of the cytoplasmic domain of Ceacam1L bound to c-Src and STAT3 and induced their phosphorylation, whereas oligomerization of this domain ablated this function. Our results suggest that Ceacam1L-dependent adhesion between GIC and surrounding cells play an essential role in GIC maintenance and proliferation, as mediated by signals transmitted by monomeric forms of the Ceacam1L cytoplasmic domain.

PMID:
26238781
DOI:
10.1158/0008-5472.CAN-15-0412
[Indexed for MEDLINE]
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