51. An Arntl2-Driven Secretome Enables Lung Adenocarcinoma Metastatic Self-Sufficiency
- Author
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Brady, Jennifer J, Chuang, Chen-Hua, Greenside, Peyton G, Rogers, Zoë N, Murray, Christopher W, Caswell, Deborah R, Hartmann, Ursula, Connolly, Andrew J, Sweet-Cordero, E Alejandro, Kundaje, Anshul, and Winslow, Monte M
- Subjects
Biochemistry and Cell Biology ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Biological Sciences ,Women's Health ,Rare Diseases ,Lung ,Genetics ,Lung Cancer ,Cancer ,2.1 Biological and endogenous factors ,1.1 Normal biological development and functioning ,ARNTL Transcription Factors ,Adenocarcinoma ,Animals ,Blotting ,Western ,CLOCK Proteins ,Calcium-Binding Proteins ,Cell Line ,Tumor ,Cell Proliferation ,Gene Expression Regulation ,Neoplastic ,Humans ,Lung Neoplasms ,Mice ,129 Strain ,Mice ,Inbred NOD ,Mice ,Knockout ,Mice ,SCID ,Neoplasm Metastasis ,RNA Interference ,Reverse Transcriptase Polymerase Chain Reaction ,Survival Analysis ,Neurosciences ,Oncology & Carcinogenesis ,Biochemistry and cell biology ,Oncology and carcinogenesis - 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.
- Published
- 2016