Axon-like protrusions promote small cell lung cancer migration and metastasis
- Stanford University School of Medicine, United States
- Tufts University, United States
Abstract
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.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files.
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Human SCLC RNA-seqUniversity of Cologne, access after IRB approval.
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Inter-tumoral heterogeneity in SCLC is influenced by the cell-type of originNCBI Gene Expression Omnibus, GSE116977.
Article and author information
Author details
Funding
National Cancer Institute (NIH R01 CA206540)
- Julien Sage
National Cancer Institute (P30 CA124435)
- Monte M Winslow
- Julien Sage
Tobacco-Related Disease Research Program (24DT-0001)
- Dian Yang
Damon Runyon Cancer Research Foundation
- Fangfei Qu
Tobacco-Related Disease Research Program
- Hongchen Cai
American Lung Association
- Chen-Hua Chuang
Pancreatic Cancer Action Network
- Barbara M Grüner
Hope Funds for Cancer Research
- Barbara M Grüner
National Cancer Institute (R00 CA207866)
- Madeleine J Oudin
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experiments were performed in accordance with Stanford University Institutional Animal Care and Use Committee guidelines (protocol number 13565).
Copyright
© 2019, Yang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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