ORCID Profile
0000-0002-1681-7491
Current Organisations
Peter MacCallum Cancer Centre
,
University of Melbourne
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Publisher: Springer Science and Business Media LLC
Date: 22-03-2023
DOI: 10.1038/S41467-023-37161-0
Abstract: In heterogeneous head and neck cancer (HNC), subtype-specific treatment regimens are currently missing. An integrated analysis of patient HNC subtypes using single-cell sequencing and proteome profiles reveals an epithelial-mesenchymal transition (EMT) signature within the epithelial cancer-cell population. The EMT signature coincides with PI3K/mTOR inactivation in the mesenchymal subtype. Conversely, the signature is suppressed in epithelial cells of the basal subtype which exhibits hyperactive PI3K/mTOR signalling. We further identify YBX1 phosphorylation, downstream of the PI3K/mTOR pathway, restraining basal-like cancer cell proliferation. In contrast, YBX1 acts as a safeguard against the proliferation-to-invasion switch in mesenchymal-like epithelial cancer cells, and its loss accentuates partial-EMT and in vivo invasion. Interestingly, phospho-YBX1 that is mutually exclusive to partial-EMT, emerges as a prognostic marker for overall patient outcomes. These findings create a unique opportunity to sensitise mesenchymal cancer cells to PI3K/mTOR inhibitors by shifting them towards a basal-like subtype as a promising therapeutic approach against HNC.
Publisher: Georg Thieme Verlag KG
Date: 28-08-2017
Abstract: Amination and amidation of aryl compounds using a transition-metal-catalyzed cross-coupling reaction typically involves prefunctionalization or preoxidation of either partner. In recent years, a new class of transition-metal-catalyzed cross-dehydrogenative coupling reaction has been developed for the direct formation of aryl C–N bonds. This short review highlights the substantial progress made for ortho-C–N bond formation via transition-metal-catalyzed chelation-directed aryl C–H activation and gives an overview of the challenges that remain for directed meta- and para-selective reactions. 1 Introduction 2 Intramolecular C–N Cross-Dehydrogenative Coupling 2.1 Nitrogen Functionality as Both Coupling Partner and Directing Group 2.2 Chelating-Group-Directed Intramolecular C–N Bond Formation 3 Intermolecular C–N Cross-Dehydrogenative Coupling 3.1 ortho-C–N Bond Formation 3.1.1 Copper-Catalyzed Reactions 3.1.2 Other Transition-Metal-Catalyzed Reactions 3.2 meta- and para-C–N Bond Formation 4 C–N Cross-Dehydrogenative Coupling of Acidic C–H Bonds 5 Conclusions
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9OB00712A
Abstract: A one-pot ortho -amination of activated arenes using sequential iron and copper catalysis has been developed and utilised for the late-stage structural ersification of biologically active 3,4-dihydroquinolin-2-ones.
Publisher: American Chemical Society (ACS)
Date: 03-07-2017
Abstract: A general and regioselective method for the chlorination of activated arenes has been developed. The transformation uses iron(III) triflimide as a powerful Lewis acid for the activation of N-chlorosuccinimide and the subsequent chlorination of a wide range of anisole, aniline, acetanilide, and phenol derivatives. The reaction was utilized for the late-stage mono- and dichlorination of a range of target compounds such as the natural product nitrofungin, the antibacterial agent chloroxylenol, and the herbicide chloroxynil. The facile nature of this transformation was demonstrated with the development of one-pot, tandem, iron-catalyzed dihalogenation processes allowing highly regioselective formation of different carbon-halogen bonds. The synthetic utility of the resulting dihalogenated aryl compounds as building blocks was established with the synthesis of natural products and pharmaceutically relevant targets.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Martyn Henry.