@article{28cacdc632cf4fdb8b847184957b1ff4,
title = "The Osteogenic Niche Is a Calcium Reservoir of Bone Micrometastases and Confers Unexpected Therapeutic Vulnerability",
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. Wang et al. report that cancer cells obtain calcium from the osteogenic niche through gap junctions and that Ca signaling together with mTOR signaling promotes bone metastasis progression. They identify that As2O3 and danusertib affect Ca signaling and preferentially target cancer cells in the bone microenvironment.",
keywords = "bone metastasis, breast cancer, calcium signaling, drug discovery or repositioning, gap junctions, microenvironment, micrometastasis, prostate cancer, the osteogenic niche, therapeutic responses",
author = "Hai Wang and Lin Tian and Jun Liu and Amit Goldstein and Igor Bado and Weijie Zhang and Arenkiel, {Benjamin R.} and Zonghai Li and Meng Yang and Shiyu Du and Hong Zhao and Rowley, {David R.} and Wong, {Stephen T.C.} and Zbigniew Gugala and Zhang, {Xiang H.F.}",
note = "Funding Information: We thank the Zhang Laboratory members for helpful input. We thank Max Wicha, Eric Chang, Dasgupta Subhamoy, Robin. L. Anderson, Thomas Westbrook, and Florent Elefteriou for reagents. X.H.-F.Z. is supported by the US Department of Defense DAMD W81XWH-16-1-0073 , NCI CA183878 , the Breast Cancer Research Foundation , and the McNair Medical Institute . H.W. is supported in part by the US Department of Defense DAMD W81XWH-13-1-0296 . X.H.-F.Z. and S.T.C.W. are supported by NIH U01188388 , NIH U54CA149196 , CPRIT RP110532-C1 , and John S Dunn Research Foundation . We also acknowledge the Pathology Core of Lester and Sue Smith Breast Center and the Dan L. Duncan Cancer Center, and Cell Sorting Core (CCSC) at Baylor College of Medicine. Funding Information: We thank the Zhang Laboratory members for helpful input. We thank Max Wicha, Eric Chang, Dasgupta Subhamoy, Robin. L. Anderson, Thomas Westbrook, and Florent Elefteriou for reagents. X.H.-F.Z. is supported by the US Department of Defense DAMD W81XWH-16-1-0073, NCI CA183878, the Breast Cancer Research Foundation, and the McNair Medical Institute. H.W. is supported in part by the US Department of Defense DAMD W81XWH-13-1-0296. X.H.-F.Z. and S.T.C.W. are supported by NIH U01188388, NIH U54CA149196, CPRIT RP110532-C1, and John S Dunn Research Foundation. We also acknowledge the Pathology Core of Lester and Sue Smith Breast Center and the Dan L. Duncan Cancer Center, and Cell Sorting Core (CCSC) at Baylor College of Medicine. Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2018",
month = nov,
day = "12",
doi = "10.1016/j.ccell.2018.10.002",
language = "English (US)",
volume = "34",
pages = "823--839.e7",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "5",
}