The Oct1 (POU2F1) transcription factor is a potent regulator of metabolism and tumorigenicity. Oct1 promotes glycolysis at the expense of mitochondrial metabolism, a metabolic profile indicative of stem cells and tumor cells. Loss of Oct1, either by germline deletion or RNAi, augments mitochondrial function and antagonizes transformation in vitro and tumor growth in vivo. Loss of Oct1 also sensitizes cells to ionizing radiation (IR), H2O2 and doxorubicin. Our new findings show that Oct1 is highly expressed in stem cells, which tend to be chemo- and radio-resistant. We have identified a pathway in which Oct1 phosphorylation couples stress inputs to transcriptional output through altered target selectivity. Our preliminary findings show that loss of Oct1 specifically depletes cancer stem cell populations as measured using two criteria. We propose to identify how Oct1 regulates metabolism and """"""""stemness"""""""" to control cancer onset and progression: 2.1.
Specific Aim 1 : Determine whether Oct1 functionally controls cancer stem cell identity 2.2.
Specific Aim 2 : Identify Oct1 activities and targets underlying the stem cell phenotype

Public Health Relevance

The most exiting aspects of this work are the potential to verify a role for Oct1 in the control of stem cell identify in adult normal and malignant cells and to identify Oct1 transcription targets that underlie the observed stem cell phenotypes. If successful, these studies will place Oct1 and components of Oct1-regulated pathways in a category of targets that may be suitable for cancer therapies. Therefore, we feel that this proposal has a strong possibility of moving the field forward.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Exploratory/Developmental Grants (R21)
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Molecular Oncogenesis Study Section (MONC)
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Mietz, Judy
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University of Utah
Schools of Medicine
Salt Lake City
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Kang, Jinsuk; Shen, Zuolian; Lim, Jae-Min et al. (2013) Regulation of Oct1/Pou2f1 transcription activity by O-GlcNAcylation. FASEB J 27:2807-17
Tantin, Dean; Voth, Warren P; Shakya, Arvind (2013) Efficient chromatin immunoprecipitation using limiting amounts of biomass. J Vis Exp :e50064
Maddox, Jessica; Shakya, Arvind; South, Samuel et al. (2012) Transcription factor Oct1 is a somatic and cancer stem cell determinant. PLoS Genet 8:e1003048
Kang, Jinsuk; Goodman, Ben; Zheng, Yixian et al. (2011) Dynamic regulation of Oct1 during mitosis by phosphorylation and ubiquitination. PLoS One 6:e23872
Ferraris, Luciana; Stewart, Allan P; Kang, Jinsuk et al. (2011) Combinatorial binding of transcription factors in the pluripotency control regions of the genome. Genome Res 21:1055-64
Shakya, Arvind; Kang, Jinsuk; Chumley, Jeffrey et al. (2011) Oct1 is a switchable, bipotential stabilizer of repressed and inducible transcriptional states. J Biol Chem 286:450-9