Zheng, YuMiyamoto, DavidWittner, BenSullivan, JamesAceto, NicolaJordan, Nicole VincentYu, MinKarabacak, NezihiComaills, ValentineMorris, RobertDesai, RushilDesai, NiyatiEmmons, ErinMilner, John D.Lee, RichardWu, Chin-LeeSequist, LeciaHaas, WilhelmTing, DavidToner, MehmetRamaswamy, SridharMaheswaran, ShyamalaHaber, Daniel2017-04-062017Zheng, Y., D. T. Miyamoto, B. S. Wittner, J. P. Sullivan, N. Aceto, N. V. Jordan, M. Yu, et al. 2017. “Expression of β-globin by cancer cells promotes cell survival during blood-borne dissemination.” Nature Communications 8 (1): 14344. doi:10.1038/ncomms14344. http://dx.doi.org/10.1038/ncomms14344.http://nrs.harvard.edu/urn-3:HUL.InstRepos:32071955Metastasis-competent circulating tumour cells (CTCs) experience oxidative stress in the bloodstream, but their survival mechanisms are not well defined. Here, comparing single-cell RNA-Seq profiles of CTCs from breast, prostate and lung cancers, we observe consistent induction of β-globin (HBB), but not its partner α-globin (HBA). The tumour-specific origin of HBB is confirmed by sequence polymorphisms within human xenograft-derived CTCs in mouse models. Increased intracellular reactive oxygen species (ROS) in cultured breast CTCs triggers HBB induction, mediated through the transcriptional regulator KLF4. Depletion of HBB in CTC-derived cultures has minimal effects on primary tumour growth, but it greatly increases apoptosis following ROS exposure, and dramatically reduces CTC-derived lung metastases. These effects are reversed by the anti-oxidant N-Acetyl Cysteine. Conversely, overexpression of HBB is sufficient to suppress intracellular ROS within CTCs. Altogether, these observations suggest that β-globin is selectively deregulated in cancer cells, mediating a cytoprotective effect during blood-borne metastasis.en-USJournal Article2017-04-0610.1038/ncomms14344