Journal article
Paracrine signaling between tumor subclones of mouse sclc: A critical role of ets transcription factor pea3 in facilitating metastasis
MC Kwon, N Proost, JY Song, KD Sutherland, J Zevenhoven, A Berns
Genes and Development | COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT | Published : 2015
Abstract
Tumor heterogeneity can create a unique symbiotic tumor microenvironment. Earlier, we showed that clonal evolution in mouse small cell lung cancer (SCLC) can result in subclones that, upon cografting, endow the neuroendocrine 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 fibroblast growth factor 2 (Fgf2) and Mapk between these diverged tumor subclones causes enhanced expression of the Pea3 (polyomavirus enhancer activator 3) transcription factor, resulting in metastatic diss..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
We thank the personnel of the animal facility for their excellent animal husbandry, P. Krimpenfort and E. Semenova for critically reading the manuscript, and A. Fish and R. Bhaskaran for technical supports. M.-C. K was a recipient of the National Research Foundation of Korea grant funded by the Korean Government (NRF-2009-352-C00133), and K.S. was a recipient of a National Health and Medical Research Council of Australia Overseas-based Biomedical Training Fellowship (no. 516781). This work was also supported by a grant of the Dutch Cancer Society and a European Research Council Synergy grant to A.B.