Activin upregulation by NF-κB is required to maintain mesenchymal features of cancer stem-like cells in non-small cell lung cancer Journal Article


Authors: Wamsley, J. J.; Kumar, M.; Allison, D. F.; Clift, S. H.; Holzknecht, C. M.; Szymura, S. J.; Hoang, S. A.; Xu, X.; Moskaluk, C. A.; Jones, D. R.; Bekiranov, S.; Mayo, M. W.
Article Title: Activin upregulation by NF-κB is required to maintain mesenchymal features of cancer stem-like cells in non-small cell lung cancer
Abstract: Soluble growth factors and cytokines within the tumor microenvironment aid in the induction of the epithelial-tomesenchymal transition (EMT). Although EMT promotes the development of cancer-initiating cells (CIC), cellular mechanisms by which cancer cells maintain mesenchymal phenotypes remain poorly understood. Work presented here indicates that induction of EMT stimulates non-small cell lung cancer (NSCLC) to secrete soluble factors that function in an autocrine fashion. Using gene expression profiling of all annotated and predicted secreted gene products, we find that NF-κB activity is required to upregulate INHBA/Activin, a morphogen in the TGFβ superfamily. INHBA is capable of inducing and maintaining mesenchymal phenotypes, including the expression of EMT master-switch regulators and self-renewal factors that sustain CIC phenotypes and promote lung metastasis. Our work demonstrates that INHBA mRNA and protein expression are commonly elevated in primary human NSCLC and provide evidence that INHBA is a critical autocrine factor that maintains mesenchymal properties of CICs to promote metastasis in NSCLC.
Keywords: controlled study; protein expression; human cell; nonhuman; protein function; mouse; disease association; gene expression; animal experiment; animal model; immunoglobulin enhancer binding protein; lung metastasis; cancer stem cell; non small cell lung cancer; molecular pathology; epithelial mesenchymal transition; human; female; article; activin a; activin a gene
Journal Title: Cancer Research
Volume: 75
Issue: 2
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 2015-01-15
Start Page: 426
End Page: 435
Language: English
DOI: 10.1158/0008-5472.can-13-2702
PROVIDER: scopus
PMCID: PMC4297542
PUBMED: 25432175
DOI/URL:
Notes: Export Date: 2 February 2015 -- Source: Scopus
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  1. David Randolph Jones
    203 Jones