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

Publication date: Available online 14 April 2016
Source:Cancer Cell
Author(s): Jennifer J. Brady, Chen-Hua Chuang, Peyton G. Greenside, Zoë N. Rogers, Christopher W. Murray, Deborah R. Caswell, Ursula Hartmann, Andrew J. Connolly, E. Alejandro Sweet-Cordero, Anshul Kundaje, Monte M. Winslow
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.

Graphical abstract

Teaser

Brady et al. identify the transcription factor Arntl2 as highly up-regulated and required for metastatic lung cancer, and high levels predict poor patient outcome. Arntl2 interacts with Clock to drive the expression of several secreted factors, including Smoc2, which is shown to have a role in metastasis.


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