Tohoku University · Biochemistry, Genetics and Molecular Biology
Professor Keito Okazaki's research lab focuses on the molecular mechanisms underlying transcriptional dysregulation in cancer, with a central emphasis on the KEAP1-NRF2 signaling pathway. The lab investigates how persistent activation of the transcription factor NRF2 contributes to tumorigenesis, therapeutic resistance, and metabolic reprogramming in non-small cell lung cancer (NSCLC), particularly through the formation of aberrant enhancers and cooperation with transcription factors like CEBPB. A key direction involves deciphering the context-dependent functions of transcription factors in cancer progression, especially in the tumor microenvironment and in disease subtypes with overlapping pathological features. The lab also explores rare renal disorders linked to monoclonal immunoglobulin deposition, highlighting the intersection of cancer biology and renal pathology.
Figures are computed from collected data and may differ slightly.
Transcriptional dysregulation, which can be caused by genetic and epigenetic alterations, is a fundamental feature of many cancers. A key cytoprotective transcriptional activator, NRF2, is often aberrantly activated in non-small cell lung cancers (NSCLCs) and supports both aggressive tumorigenesis and therapeutic resistance. Herein, we find that persistently activated NRF2 in NSCLCs generates enhancers at gene loci that are not normally regulated by transiently activated NRF2 under physiological
The KEAP1-NRF2 system is a sulfur-employing defense mechanism against oxidative and electrophilic stress. NRF2 is a potent transcription activator for genes mediating sulfur-involving redox reactions, and KEAP1 controls the NRF2 activity in response to the stimuli by utilizing reactivity of sulfur atoms. In many human cancer cells, the KEAP1-mediated regulation of NRF2 activity is abrogated, resulting in the persistent activation of NRF2. Persistently activated NRF2 drives malignant progression
NRF2 is a transcription activator that plays a key role in cytoprotection against oxidative stress. Although increased NRF2 activity is principally beneficial for our health, NRF2 activation in cancer cells is detrimental, as it drives their malignant progression. We previously found that CCAAT/enhancer-binding protein B (CEBPB) cooperates with NRF2 in NRF2-activated lung cancer and enhances tumour-initiating activity by promoting NOTCH3 expression. However, the general contribution of CEBPB in
Summary Transcriptional dysregulation, which can be caused by genetic and epigenetic alterations, is a fundamental feature of many cancers. A key cytoprotective transcriptional activator, NRF2, is often aberrantly activated in non-small cell lung cancers (NSCLCs) and supports both aggressive tumorigenesis and therapeutic resistance. Herein, we found that persistently activated NRF2 in NSCLCs generates enhancers at gene loci that are not normally regulated by transiently activated NRF2 under phys
A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-20927-9.
Abstract Regnase-1, encoded by the ZC3H12A gene, is a well-known RNase that suppresses inflammation by degrading the mRNAs of inflammatory cytokines. However, its role in cancer pathogenesis, especially in non-small cell lung cancer (NSCLC), remains poorly understood. Through an analysis of public databases, we found that NSCLC patients with higher ZC3H12A expression levels had a worse prognosis than those with lower levels. To explore the function of Regnase-1 in NSCLC, we knocked out the ZC3H1
Regnase-1, encoded by the ZC3H12A gene, is a well-known RNase that suppresses inflammation by degrading the mRNAs of inflammatory cytokines. However, its role in cancer pathogenesis, especially in non-small cell lung cancer (NSCLC), remains poorly understood. Through an analysis of public databases, we found that NSCLC patients with higher ZC3H12A expression levels had a worse prognosis than those with lower levels. To explore the function of Regnase-1 in NSCLC, we knocked out the ZC3H12A gene i
Sulfur, like oxygen, belongs to Group 16 of the periodic table and is characterized by its flexibility in both donating and accepting electrons, as well as its wide range of oxidation states. These properties enable sulfur to participate in diverse redox reactions. In biological systems, sulfur plays vital roles as a component of catalytic centers of enzymes and as a redox sensor. Moreover, sulfur is the only element known to form stable linear chains through homoelemental bonding, a phenomenon
Light chain-only variant of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID-LC) and light chain deposition disease (LCDD) are both renal disorders caused by the overproduction of monoclonal immunoglobulin light chains and their deposition in renal tissues. However, the renal pathological features of these two entities are characteristically distinct. We report a rare case of multiple myeloma presenting with renal pathology exhibiting overlapping features of both
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