Expression of β-globin by cancer cells promotes cell survival during blood-borne dissemination

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Expression of β-globin by cancer cells promotes cell survival during blood-borne dissemination

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Title: Expression of β-globin by cancer cells promotes cell survival during blood-borne dissemination
Author: Zheng, Yu; Miyamoto, David T.; Wittner, Ben S.; Sullivan, James P.; Aceto, Nicola; Jordan, Nicole Vincent; Yu, Min; Karabacak, Nezihi Murat; Comaills, Valentine; Morris, Robert; Desai, Rushil; Desai, Niyati; Emmons, Erin; Milner, John D.; Lee, Richard J.; Wu, Chin-Lee; Sequist, Lecia V.; Haas, Wilhelm; Ting, David T.; Toner, Mehmet; Ramaswamy, Sridhar; Maheswaran, Shyamala; Haber, Daniel A.

Note: Order does not necessarily reflect citation order of authors.

Citation: Zheng, 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.
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Abstract: Metastasis-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.
Published Version: doi:10.1038/ncomms14344
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321792/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:32071955
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