Axon-like protrusions promote small cell lung cancer migration and metastasis

• Published in: eLife Vol. 8
• Main Authors: Yang, Dian, Qu, Fangfei, Cai, Hongchen, Chuang, Chen-Hua, Lim, Jing Shan, Jahchan, Nadine, Grüner, Barbara M, S Kuo, Christin, Kong, Christina, Oudin, Madeleine J, Winslow, Monte M, Sage, Julien
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 13-12-2019; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Animals; Axon guidance; Axonogenesis; Cancer; Cancer Biology; Cancer cells; Cancer metastasis; Cell Biology; Cell culture; Cell migration; Cell Movement; Cell Surface Extensions - metabolism; Death; Experiments; Gene expression; Genes; Health aspects; Humans; Liver; Lung cancer; Lung Neoplasms - physiopathology; Metastases; Metastasis; Mice; migration; Neoplasm Metastasis - physiopathology; neuroendocrine; neuronal; Neurons; Novels; Patients; protrusions; Scientific equipment industry; SCLC; Small cell lung cancer; Small cell lung carcinoma; Small Cell Lung Carcinoma - physiopathology; Tumor Cells, Cultured; Tumors; Canada; United States; SCLC; mouse; cell biology; neuroendocrine; metastasis; neuronal; migration; cancer biology; human; protrusions
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.50616

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.