@article{40bab53bf9dc4696971e76741f3d93ce,
title = "Scavenging of Labile Heme by Hemopexin Is a Key Checkpoint in Cancer Growth and Metastases",
abstract = "Canesin et al. describe a role and mechanism for labile heme as a key player in regulating gene expression to promote carcinogenesis via binding to G-quadruplex in the c-MYC promoter. Hemopexin, a heme scavenger, may be used as a strategy to block progression of cancer.",
keywords = "DNA G-quadruplexes, c-myc, heme, heme oxygenase-1, hemopexin, metastases, prostate cancer",
author = "Giacomo Canesin and {Di Ruscio}, Annalisa and Mailin Li and Simone Ummarino and Andreas Hedblom and Reeham Choudhury and Agnieszka Krzyzanowska and Eva Csizmadia and Macarena Palominos and Anna Stiehm and Alexander Ebralidze and Chen, {Shao Yong} and Bassal, {Mahmoud A.} and Ping Zhao and Emanuela Tolosano and Laurence Hurley and Anders Bjartell and Tenen, {Daniel G.} and Barbara Wegiel",
note = "Funding Information: Our studies were supported by funding from NCI R21 CA169904 and NIDDK R01 DK104714 to B.W.; NCI R00 CA188595 to A.D.R.; the Giovanni Armenise-Harvard Foundation Career Development Award and the Italian Association for Cancer Research (AIRC) Start-up Grant N.15347 to A.D.R.; Swedish Childhood Cancer Foundation grant to A.H.; NCI R35CA197697 and P01HL131477 to D.G.T. D.G.T. was supported by a STaR Investigator Award from the National Medical Research Council of the Singapore Ministry of Health. B.W. is a lecturer at Aston University in the UK. We thank Dr. Kenneth Swanson (BIDMC/HMS, Boston, MA) for helpful discussions about the project. We thank Dr. Balasubramanian (UK) for providing a plasmid-encoding single-chain BG4, Dr. Weinberg (MIT, Cambridge, MA) for BJ fibroblasts. Dr. Dizeyi (Lund University, Malmo, Sweden) for PNT1A cell line and Dr. Balk (BIDMC/HMS, Boston, MA) for PC3 cells. We are grateful to Dr. Hamza (University of Maryland, MD) for providing APX-NLS and control plasmids. G.C. A.D.R. M.L. and B.W. designed the study. M.L. and B.W. conceived the original idea and acquired an original set of in vitro and in vivo data using PC3 xenograft models. A.D.R. performed electrophoretic mobility shift assay (EMSA) experiments. G.C. and B.W. performed in vivo experiments and analyses of TMA. S.U. did the ChIP assays. S.-Y.C. helped with the ChIP protocol. E.C. performed immunohistochemistry (IHC) and immunofluorescence (IF) staining. A.H. and R.C. performed colony assays with genetic quality control (GQC) and part of the western blots. A.K. M.P. and A.S. performed TMA staining and analyzed the data. L.H. and P.Z. performed CD experiments and provided reagents for the G4 study. M.A.B. analyzed the RNA-seq data. D.G.T. and A.E. provided input on c-myc regulation and EMSA. E.T. provided Hx knockout (KO) mice. M.L. G.C. A.D.R. and B.W. wrote the paper with input from all authors. B.W. supervised the work. The authors declare no competing interests. Funding Information: Our studies were supported by funding from NCI R21 CA169904 and NIDDK R01 DK104714 to B.W.; NCI R00 CA188595 to A.D.R.; the Giovanni Armenise-Harvard Foundation Career Development Award and the Italian Association for Cancer Research (AIRC) Start-up Grant N.15347 to A.D.R.; Swedish Childhood Cancer Foundation grant to A.H.; NCI R35CA197697 and P01HL131477 to D.G.T. D.G.T. was supported by a STaR Investigator Award from the National Medical Research Council of the Singapore Ministry of Health. B.W. is a lecturer at Aston University in the UK. We thank Dr. Kenneth Swanson (BIDMC/HMS, Boston, MA) for helpful discussions about the project. We thank Dr. Balasubramanian (UK) for providing a plasmid-encoding single-chain BG4, Dr. Weinberg (MIT, Cambridge, MA) for BJ fibroblasts. Dr. Dizeyi (Lund University, Malmo, Sweden) for PNT1A cell line and Dr. Balk (BIDMC/HMS, Boston, MA) for PC3 cells. We are grateful to Dr. Hamza (University of Maryland, MD) for providing APX-NLS and control plasmids. Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = sep,
day = "22",
doi = "10.1016/j.celrep.2020.108181",
language = "English (US)",
volume = "32",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "12",
}