Journal article

The functional GRHL3-filaggrin axis maintains a tumor differentiation potential and influences drug sensitivity

Yuchen Bai, Zixuan Zhao, Jarryd Boath, Bryce J van denderen, Charbel Darido

MOLECULAR THERAPY | CELL PRESS | Published : 2021

Abstract

Current therapies for treating heterogeneous cancers such as head and neck squamous cell carcinoma (HNSCC) are non-selective and are administered independent of response biomarkers. Therapy resistance subsequently emerges, resulting in increased cellular proliferation that is associated with loss of differentiation. Whether a cancer cell differentiation potential can dictate therapy responsiveness is still currently unknown. A multi-omic approach integrating whole-genome and whole-transcriptome sequencing with drug sensitivity was employed in a HNSCC mouse model, primary patients' data, and human cell lines to assess the potential of functional differentiation in predicting therapy response...

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Grants

Awarded by Australian National Health and Medical Research Council (NHMRC)


Awarded by Victorian Cancer Agency Mid-Career Fellowship


Funding Acknowledgements

The authors would like to acknowledge the assistance of Jason Li from the Peter MacCallum Cancer Centre Bioinformatics Core Facility. The RNA polymerase I inhibitor CX-546153 was kindly provided by Professor Rick Pearson (PMCC, Melbourne). The STAT3 inhibitor Niclosamide54 and the c-Myc inhibitor JQ1 were kindly provided by Dr. Rodney Luwor (Royal Melbourne Hospital, Melbourne). The MAP kinase-interacting serine/threonine kinases 1 and 2 (MNK1/2) inhibitor SEL20155 was provided by SELVITA through an MTA with the assistance of Dr. Luke Furic. This research was supported by a grant from the Australian National Health and Medical Research Council (NHMRC; APP1106697) and a Victorian Cancer Agency Mid-Career Fellowship (MCRF16017) to C.D.