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Cancer Cell. 2016 May 9;29(5):697-710. doi: 10.1016/j.ccell.2016.03.003. Epub 2016 Apr 14.

An Arntl2-Driven Secretome Enables Lung Adenocarcinoma Metastatic Self-Sufficiency.

Author information

1
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
2
Biomedical Informatics Training Program, Stanford University School of Medicine, Stanford, CA 94305, USA.
3
Cancer Biology Program, Stanford University School of Medicine, Stanford, CA 94305, USA.
4
Center for Biochemistry, University of Cologne, 50931 Cologne, Germany.
5
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
6
Cancer Biology Program, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
7
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Computer Science, Stanford University, Stanford, CA 94305, USA.
8
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Cancer Biology Program, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: mwinslow@stanford.edu.

Abstract

The ability of cancer cells to establish lethal metastatic lesions requires the survival and expansion of single cancer cells at distant sites. The factors controlling the clonal growth ability of individual cancer cells remain poorly understood. Here, we show that high expression of the transcription factor ARNTL2 predicts poor lung adenocarcinoma patient outcome. Arntl2 is required for metastatic ability in vivo and clonal growth in cell culture. Arntl2 drives metastatic self-sufficiency by orchestrating the expression of a complex pro-metastatic secretome. We identify Clock as an Arntl2 partner and functionally validate the matricellular protein Smoc2 as a pro-metastatic secreted factor. These findings shed light on the molecular mechanisms that enable single cancer cells to form allochthonous tumors in foreign tissue environments.

PMID:
27150038
PMCID:
PMC4864124
DOI:
10.1016/j.ccell.2016.03.003
[Indexed for MEDLINE]
Free PMC Article

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