The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites

Hua Gao, Goutam Chakraborty, Ai Ping Lee-Lim, Qianxing Mo, Markus Decker, Alin Vonica, Ronglai Shen, Edi Brogi, Ali H. Brivanlou, Filippo G. Giancotti

Research output: Contribution to journalArticlepeer-review

332 Scopus citations

Abstract

The mechanistic underpinnings of metastatic dormancy and reactivation are poorly understood. A gain-of-function cDNA screen reveals that Coco, a secreted antagonist of TGF-β ligands, induces dormant breast cancer cells to undergo reactivation in the lung. Mechanistic studies indicate that Coco exerts this effect by blocking lung-derived BMP ligands. Whereas Coco enhances the manifestation of traits associated with cancer stem cells, BMP signaling suppresses it. Coco induces a discrete gene expression signature, which is strongly associated with metastatic relapse to the lung, but not to the bone or brain in patients. Experiments in mouse models suggest that these latter organs contain niches devoid of bioactive BMP. These findings reveal that metastasis-initiating cells need to overcome organ-specific antimetastatic signals in order to undergo reactivation.

Original languageEnglish
Pages (from-to)764-779
Number of pages16
JournalCell
Volume150
Issue number4
DOIs
StatePublished - 17 Aug 2012
Externally publishedYes

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