American Association for Cancer Research
00085472can181972-sup-204269_3_supp_5145609_pl7l2h.pdf (247.47 kB)

Supplementary Figure S5. Quantification of Western blot bands using Image J. from STING Promotes Homeostasis via Regulation of Cell Proliferation and Chromosomal Stability

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journal contribution
posted on 2023-03-31, 03:07 authored by Diana Rose E. Ranoa, Ryan C. Widau, Stephen Mallon, Akash D. Parekh, Claudia M. Nicolae, Xiaona Huang, Michael J. Bolt, Ainhoa Arina, Renate Parry, Stephen J. Kron, George-Lucian Moldovan, Nikolai N. Khodarev, Ralph R. Weichselbaum

The pixel units obtained for each protein band from Western gels shown in Main Figures 4B (A), 4C (B), 4D (C), and 4E (D) was normalized to the pixel units calculated from their respective b-Actin loading control. For phosphorylated proteins, we then quantified the fraction of phosphorylated proteins to the absolute total amount of protein (total protein + phosphorylated protein). For dose-dependent and stimulation assays, the variables tested were normalized to their respective wild-type unstimulated controls.


Ludwig Center for Metastasis Research

Virginia and Ludwig Foundation for Cancer Research

Lung Cancer Research Foundation




Given the integral role of stimulator of interferon genes (STING, TMEM173) in the innate immune response, its loss or impairment in cancer is thought to primarily affect antitumor immunity. Here we demonstrate a role for STING in the maintenance of cellular homeostasis through regulation of the cell cycle. Depletion of STING in human and murine cancer cells and tumors resulted in increased proliferation compared with wild-type controls. Microarray analysis revealed genes involved in cell-cycle regulation are differentially expressed in STINGko compared with WT MEFs. STING-mediated regulation of the cell cycle converged on NFκB- and p53-driven activation of p21. The absence of STING led to premature activation of cyclin-dependent kinase 1 (CDK1), early onset to S-phase and mitosis, and increased chromosome instability, which was enhanced by ionizing radiation. These results suggest a pivotal role for STING in maintaining cellular homeostasis and response to genotoxic stress. These findings provide clear mechanistic understanding of the role of STING in cell-cycle regulation, which may be exploited in cancer therapy because most normal cells express STING, while many tumor cells do not.See related commentary by Gius and Zhu, p. 1295