Axon-like protrusions promote small cell lung cancer migration and metastasis
Dian Yang,
Fangfei Qu,
Hongchen Cai,
Chen-Hua Chuang,
Jing Shan Lim,
Nadine Jahchan,
Barbara M Grüner,
Christin S Kuo,
Christina Kong,
Madeleine J Oudin,
Monte M Winslow,
Julien Sage
Affiliations
Dian Yang
Cancer Biology Program, Stanford University School of Medicine, Stanford, United States; Department of Pediatrics, Stanford University School of Medicine, Stanford, United States; Department of Genetics, Stanford University School of Medicine, Stanford, United States
Fangfei Qu
Department of Pediatrics, Stanford University School of Medicine, Stanford, United States; Department of Genetics, Stanford University School of Medicine, Stanford, United States
Hongchen Cai
Department of Genetics, Stanford University School of Medicine, Stanford, United States
Chen-Hua Chuang
Department of Genetics, Stanford University School of Medicine, Stanford, United States
Jing Shan Lim
Cancer Biology Program, Stanford University School of Medicine, Stanford, United States; Department of Pediatrics, Stanford University School of Medicine, Stanford, United States; Department of Genetics, Stanford University School of Medicine, Stanford, United States
Nadine Jahchan
Department of Pediatrics, Stanford University School of Medicine, Stanford, United States; Department of Genetics, Stanford University School of Medicine, Stanford, United States
Department of Genetics, Stanford University School of Medicine, Stanford, United States; Department of Pathology, Stanford University School of Medicine, Stanford, United States; Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany; German Cancer Consortium (DKTK) partner site Essen, Essen, Germany
Christin S Kuo
Department of Pediatrics, Stanford University School of Medicine, Stanford, United States
Christina Kong
Department of Pathology, Stanford University School of Medicine, Stanford, United States
Madeleine J Oudin
Department of Biomedical Engineering, Tufts University, Medford, United States
Monte M Winslow
Cancer Biology Program, Stanford University School of Medicine, Stanford, United States; Department of Genetics, Stanford University School of Medicine, Stanford, United States; Department of Pathology, Stanford University School of Medicine, Stanford, United States
Cancer Biology Program, Stanford University School of Medicine, Stanford, United States; Department of Pediatrics, Stanford University School of Medicine, Stanford, United States; Department of Genetics, Stanford University School of Medicine, Stanford, United States
Metastasis is the main cause of death in cancer patients but remains a poorly understood process. Small cell lung cancer (SCLC) is one of the most lethal and most metastatic cancer types. SCLC cells normally express neuroendocrine and neuronal gene programs but accumulating evidence indicates that these cancer cells become relatively more neuronal and less neuroendocrine as they gain the ability to metastasize. Here we show that mouse and human SCLC cells in culture and in vivo can grow cellular protrusions that resemble axons. The formation of these protrusions is controlled by multiple neuronal factors implicated in axonogenesis, axon guidance, and neuroblast migration. Disruption of these axon-like protrusions impairs cell migration in culture and inhibits metastatic ability in vivo. The co-option of developmental neuronal programs is a novel molecular and cellular mechanism that contributes to the high metastatic ability of SCLC.
