title: An Arntl2-Driven Secretome Enables Lung Adenocarcinoma Metastatic Self-Sufficiency.
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.
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Brady
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Chen-Hua
authors.initials: CH
authors.lastname: Chuang
authors.affiliation: Biomedical Informatics Training Program, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Peyton G
authors.initials: PG
authors.lastname: Greenside
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Zoë N
authors.initials: ZN
authors.lastname: Rogers
authors.affiliation: Cancer Biology Program, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Murray
authors.affiliation: Cancer Biology Program, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Deborah R
authors.initials: DR
authors.lastname: Caswell
authors.affiliation: Center for Biochemistry, University of Cologne, 50931 Cologne, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Hartmann
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Connolly
authors.affiliation: 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.
authors.forename: E Alejandro
authors.initials: EA
authors.lastname: Sweet-Cordero
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Computer Science, Stanford University, Stanford, CA 94305, USA.
authors.forename: Anshul
authors.initials: A
authors.lastname: Kundaje
authors.affiliation: 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.
authors.forename: Monte M
authors.initials: MM
authors.lastname: Winslow
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D057507:Mice, 129 Strain; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis
chemical_list: D056930:ARNTL Transcription Factors; C486615:BMAL2 protein, human; D002135:Calcium-Binding Proteins; C476827:SMOC2 protein, human; D056926:CLOCK Proteins