Publications

@article{Almozyan2021-jt,

title = {FLYWCH1, a multi-functional zinc finger protein contributes to 

 the DNA repair pathway},

author = {Sheema Almozyan and James Coulton and Roya Babaei-Jadidi and Abdolrahman S Nateri},

year  = {2021},

date = {2021-04-01},

journal = {Cells},

volume = {10},

number = {4},

pages = {889},

publisher = {MDPI AG},

abstract = {Over recent years, several Cys2-His2 (C2H2) domain-containing 

 proteins have emerged as critical players in repairing 

 DNA-double strand breaks. Human FLYWCH1 is a newly characterised 

 nuclear transcription factor with (C2H2)-type zinc-finger 

 DNA-binding domains. Yet, our knowledge about FLYWCH1 is still 

 in its infancy. This study explores the expression, role and 

 regulation of FLYWCH1 in the context of DNA damage and repair. 

 We provide evidence suggesting a potential contribution of 

 FLYWCH1 in facilitating the recruitment of DNA-damage response 

 proteins (DDRPs). We found that FLYWCH1 colocalises with 

 γH2AX in normal fibroblasts and colorectal cancer (CRC) 

 cell lines. Importantly, our results showed that enforced 

 expression of FLYWCH1 induces the expression of γH2AX, 

 ATM and P53 proteins. Using an ATM-knockout (ATMKO) model, we 

 indicated that FLYWCH1 mediates the phosphorylation of H2AX 

 (Ser139) independently to ATM expression. On the other hand, the 

 induction of DNA damage using UV-light induces the endogenous 

 expression of FLYWCH1. Conversely, cisplatin treatment reduces 

 the endogenous level of FLYWCH1 in CRC cell lines. Together, our 

 findings uncover a novel FLYWCH1/H2AX phosphorylation axis in 

 steady-state conditions and during the induction of the 

 DNA-damage response (DDR). Although the role of FLYWCH1 within 

 the DDR machinery remains largely uncharacterised and poorly 

 understood, we here report for the first-time findings that 

 implicate FLYWCH1 as a potential participant in the DNA damage 

 response signaling pathways.},

keywords = {ATM, CRC, Cys2-His2 (C2H2)-type zinc-finger, DNA-damage   response, FLYWCH1, p53, γH2AX},

pubstate = {published},

tppubtype = {article}

}

@article{Ahmed2019-eb,

title = {Repurposing antibacterial AM404 as a potential anticancer drug 

 for targeting colorectal cancer stem-like cells},

author = {Mehreen Ahmed and Nicholas Jinks and Roya Babaei-Jadidi and Hossein Kashfi and Marcos Castellanos-Uribe and Sean T May and Abhik Mukherjee and Abdolrahman S Nateri},

year  = {2019},

date = {2019-12-01},

journal = {Cancers (Basel)},

volume = {12},

number = {1},

pages = {106},

publisher = {MDPI AG},

abstract = {Tumour-promoting inflammation is involved in colorectal cancer 

 (CRC) development and therapeutic resistance. However, the 

 antibiotics and antibacterial drugs and signalling that regulate 

 the potency of anticancer treatment upon forced differentiation 

 of cancer stem-like cell (CSC) are not fully defined yet. We 

 screened an NIH-clinical collection of the small-molecule 

 compound library of antibacterial/anti-inflammatory agents that 

 identified potential candidate drugs targeting CRC-SC for 

 differentiation. Selected compounds were validated in both in 

 vitro organoids and ex vivo colon explant models for their 

 differentiation induction, impediment on neoplastic cell growth, 

 and to elucidate the mechanism of their anticancer activity. We 

 initially focused on AM404, an anandamide uptake inhibitor. 

 AM404 is a metabolite of acetaminophen with antibacterial 

 activity, which showed high potential in preventing CRC-SC 

 features, such as stemness/de-differentiation, migration and 

 drug-resistance. Furthermore, AM404 suppressed the expression of 

 FBXL5 E3-ligase, where AM404 sensitivity was mimicked by 

 FBXL5-knockout. This study uncovers a new molecular mechanism 

 for AM404-altering FBXL5 oncogene which mediates 

 chemo-resistance and CRC invasion, thereby proposes to repurpose 

 antibacterial AM404 as an anticancer agent.},

keywords = {AM404, cancer stem cells, colonosphere, CRC, Differentiation, drug screening, FBXL5 E3-ligase, patient derived organoids, resistance and metastasis, tissue explants},

pubstate = {published},

tppubtype = {article}

}