Expression of β-globin by cancer cells promotes cell survival during blood-borne dissemination
Jordan, Nicole Vincent
Milner, John D.
MetadataShow full item record
CitationZheng, 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.
AbstractMetastasis-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.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:32071955
- HMS Scholarly Articles