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

• Main Authors: 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
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2019-12-01
• Series: eLife
• Subjects: SCLC; neuroendocrine; neuronal; protrusions; migration; metastasis
• Online Access: https://elifesciences.org/articles/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.