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Supplementary Table Legend from Computational Identification of a p38SAPK-Regulated Transcription Factor Network Required for Tumor Cell Quiescence

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posted on 2023-03-30, 18:44 authored by Alejandro P. Adam, Ajish George, Denis Schewe, Paloma Bragado, Bibiana V. Iglesias, Aparna C. Ranganathan, Antonis Kourtidis, Douglas S. Conklin, Julio A. Aguirre-Ghiso
Supplementary Table Legend from Computational Identification of a p38SAPK-Regulated Transcription Factor Network Required for Tumor Cell Quiescence

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ARTICLE ABSTRACT

The stress-activated kinase p38 plays key roles in tumor suppression and induction of tumor cell dormancy. However, the mechanisms behind these functions remain poorly understood. Using computational tools, we identified a transcription factor (TF) network regulated by p38α/β and required for human squamous carcinoma cell quiescence in vivo. We found that p38 transcriptionally regulates a core network of 46 genes that includes 16 TFs. Activation of p38 induced the expression of the TFs p53 and BHLHB3, while inhibiting c-Jun and FoxM1 expression. Furthermore, induction of p53 by p38 was dependent on c-Jun down-regulation. Accordingly, RNAi down-regulation of BHLHB3 or p53 interrupted tumor cell quiescence, while down-regulation of c-Jun or FoxM1 or overexpression of BHLHB3 in malignant cells mimicked the onset of quiescence. Our results identify components of the regulatory mechanisms driving p38-induced cancer cell quiescence. These may regulate dormancy of residual disease that usually precedes the onset of metastasis in many cancers. [Cancer Res 2009;69(14):5664–72]

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