| Literature DB >> 30423299 |
Hai Wang1, Lin Tian2, Jun Liu1, Amit Goldstein1, Igor Bado1, Weijie Zhang1, Benjamin R Arenkiel3, Zonghai Li4, Meng Yang5, Shiyu Du6, Hong Zhao7, David R Rowley8, Stephen T C Wong9, Zbigniew Gugala10, Xiang H-F Zhang11.
Abstract
The fate of disseminated tumor cells is largely determined by microenvironment (ME) niche. The osteogenic niche promotes cancer cell proliferation and bone metastasis progression. We investigated the underlying mechanisms using pre-clinical models and analyses of clinical data. We discovered that the osteogenic niche serves as a calcium (Ca) reservoir for cancer cells through gap junctions. Cancer cells cannot efficiently absorb Ca from ME, but depend on osteogenic cells to increase intracellular Ca concentration. The Ca signaling, together with previously identified mammalian target of rapamycin signaling, promotes bone metastasis progression. Interestingly, effective inhibition of these pathways can be achieved by danusertib, or a combination of everolimus and arsenic trioxide, which provide possibilities of eliminating bone micrometastases using clinically established drugs.Entities:
Keywords: bone metastasis; breast cancer; calcium signaling; drug discovery or repositioning; gap junctions; microenvironment; micrometastasis; prostate cancer; the osteogenic niche; therapeutic responses
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Year: 2018 PMID： 30423299 PMCID： PMC6239211 DOI： 10.1016/j.ccell.2018.10.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743