Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, United States
Jing Wang
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, United States; Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, United States
Clare M Adams
Department of Cancer Biology, Thomas Jefferson University, Philadelphia, United States
Gregory Caleb Howard
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, United States
Simona G Codreanu
Center for Innovative Technology (CIT), Vanderbilt University, Nashville, United States; Department of Chemistry, Vanderbilt University, Nashville, United States
Center for Innovative Technology (CIT), Vanderbilt University, Nashville, United States; Department of Chemistry, Vanderbilt University, Nashville, United States
John A McLean
Center for Innovative Technology (CIT), Vanderbilt University, Nashville, United States; Department of Chemistry, Vanderbilt University, Nashville, United States
Lance R Thomas
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, United States
Shelly L Lorey
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, United States
Yuichi J Machida
Department of Oncology, Mayo Clinic, Rochester, United States
April M Weissmiller
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, United States
Department of Cancer Biology, Thomas Jefferson University, Philadelphia, United States
Qi Liu
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, United States; Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, United States
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, United States; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, United States
The oncoprotein transcription factor MYC is a major driver of malignancy and a highly validated but challenging target for the development of anticancer therapies. Novel strategies to inhibit MYC may come from understanding the co-factors it uses to drive pro-tumorigenic gene expression programs, providing their role in MYC activity is understood. Here we interrogate how one MYC co-factor, host cell factor (HCF)–1, contributes to MYC activity in a human Burkitt lymphoma setting. We identify genes connected to mitochondrial function and ribosome biogenesis as direct MYC/HCF-1 targets and demonstrate how modulation of the MYC–HCF-1 interaction influences cell growth, metabolite profiles, global gene expression patterns, and tumor growth in vivo. This work defines HCF-1 as a critical MYC co-factor, places the MYC–HCF-1 interaction in biological context, and highlights HCF-1 as a focal point for development of novel anti-MYC therapies.
