Roles of RUNX in Solid Tumors
All RUNX genes have been implicated in the development of solid tumors, but the role each RUNX gene plays in the different tumor types is complicated by multiple interactions with major signaling pathways and tumor heterogeneity. Moreover, for a given tis
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Linda Shyue Huey Chuang, Kosei Ito, and Yoshiaki Ito
Abstract
All RUNX genes have been implicated in the development of solid tumors, but the role each RUNX gene plays in the different tumor types is complicated by multiple interactions with major signaling pathways and tumor heterogeneity. Moreover, for a given tissue type, the specific role of each RUNX protein is distinct at different stages of differentiation. A regulatory function for RUNX in tissue stem cells points sharply to a causal effect in tumorigenesis. Understanding how RUNX dysregulation in cancer impinges on normal biological processes is important for identifying the molecular mechanisms that lead to malignancy. It will also indicate whether restoration of proper RUNX function to redirect cell fate is a feasible treatment for cancer. With the recent advances in RUNX research, it is time to revisit the many mechanisms/pathways that RUNX engage to regulate cell fate and decide whether cells proliferate, differentiate or die. Keywords
RUNX • Solid tumors • Tumor suppressor • Oncogene • Wnt • TGFβ • RAS • Senescence • Protein-protein interaction • Stress-inducible gene • Precancerous state • Intestinal metaplasia
19.1 Introduction L.S.H. Chuang • Y. Ito (*) Cancer Science Institute of Singapore, Center for Translational Medicine, National University of Singapore, 14 Medical Drive #12-01, Singapore 117599, Singapore e-mail: [email protected] K. Ito Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan
The past decade has seen considerable progress in our understanding of the RUNX family of transcription factors in solid tumors. There are three mammalian RUNX genes and all have been directly implicated at various stages of tumor development, including initiation, progression and invasion. Animal knockout models of individual Runx genes revealed distinct developmental
© Springer Nature Singapore Pte Ltd. 2017 Y. Groner et al. (eds.), RUNX Proteins in Development and Cancer, Advances in Experimental Medicine and Biology 962, DOI 10.1007/978-981-10-3233-2_19
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defects in hematopoiesis, bone development, the gastronintestinal tract and neurogenesis. While these findings reflect the tissue-specific expression and function of RUNX1 in the hematopoietic system, RUNX2 in bone, and RUNX3 in the gastrointestinal tract, lymphocytes as well as the dorsal root ganglion (DRG) neuron, it is noteworthy that all RUNX proteins are expressed in a broad range of tissues (Ito et al. 2015). Moreover, RUNX expression patterns are extremely dynamic and depend on the stage of differentiation as well as developmental and environmental cues. Because of the conserved Runt and the divergent C-terminal domains, RUNX proteins act redundantly in some cellular contexts and exert unique effects in others. This review summarizes the role of RUNX in solid tumors. This is by no means an exhaustive review for many types of cancer. Because of the focus of our laboratory, we will describe in detail our analyses of RUNX3 funct
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