Research Publications

Kwon MC et al. Genes Dev. 2015 Aug 1;29(15)1587. Paracrine signaling between tumor subclones of mouse SCLC: a critical role of

Year of publication
16 Sep 2015 10:32
Genes and Development 2015 Aug 1;29(15):1587-92

Paracrine signaling between tumor subclones of mouse SCLC; a critical role of Ets transcription factor Pea3 in facilitating metastasis

Min-chul Kwon1, Natalie Proost1, Ji-Ying Song2, Kate Sutherland1, 3, John Zevenhoven1, Anton Berns1, 41Division of Molecular Genetics, 2Department of Experimental Animal Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands

4Skolkovo Institute of Science and Technology, Skolkovo Innovation Center, Building 5, Moscow 143026, Russia

3Current address: Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research (The University of Melbourne), 1G Royal Parade, Parkville 3052, Australia.

Tumor heterogeneity can create a unique symbiotic tumor-microenvironment. Earlier we have shown that clonal evolution in mouse SCLC can result in subclones that upon co-grafting endow the neuroendocrine (NE) tumor cells with metastatic potential. We now show that paracrine signaling between SCLC subclones is a critical requirement in the early steps of the metastatic process, such as local invasion and intravasation. We further show evidence that  paracrine signaling via Fgf2 and MAPK between these diverged tumor subclones causes enhanced expression of the Pea3 transcription factor resulting in metastatic dissemination of the NE tumor subclones. Our data reveal for the first time paracrine signaling between tumor cell subclones in SCLC resulting in metastatic spread of SCLC.


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