2022 Fiscal Year Annual Research Report
Targeting MiT transcription factors as a novel therapeutic approach to disru pt the adaptive response to microenvironmental stresses that gives rise to d ormant and cancer stem cell
| Project/Area Number |
21K15524
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Keywords | Dormancy / PDAC / TFEB / TFE3 / Phenotypic heterogeneity / Plasticity / ISR |
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| Outline of Annual Research Achievements |
To understand how TFE3/B contribute to adaptive responses leading to generation of dormant and quiescence cancer cells, I applied a combination of molecular techniques including siRNA, shRNA and CRISPR/Cas9 KO of TFE3/B in a number of PDAC cell lines with very different phenotype and performed metabolic, proliferation studies and sensitivity to current standard chemotherapies. Through a combination of RNA-seq and ChIP-seq I have profiled TFE3/B contribution to microenvironmental stress over time.
Using OSCAR reporter, I demonstrated phenotypic heterogeneity and the presence of transcription quiescence cells (a hallmark of dormancy) even among isogenic population (Cell lines) and demonstrated that, at least in vitro, standard chemotherapy leads to an increased in this dormant population.
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