Biology subjects

Sim, Y.

Publications and source records attributed to Sim, Y..

2 recordsLinked to original sources

bioRxiv2024

TWEAK/Fn14 signalling driven super-enhancer reprogramming promotes pro-metastatic metabolic rewiring in Triple-Negative Breast Cancer

Triple Negative Breast Cancer (TNBC) is the most aggressive breast cancer subtype suffering from limited targeted treatment options. Following recent reports correlating Fn14 receptor overexpression in ER-negative breast cancers with metastatic events, we show that Fn14 is specifically overexpressed in TNBC patients and associated with poor survival. We demonstrate that constitutive Fn14 signalling rewires the transcriptomic and epigenomic landscape of TNBC, leading to enhanced tumour growth and metastasis. We further illustrate that such mechanisms activate TNBC-specific super enhancers (SE) to drive the transcriptional activation of cancer dependency genes via chromatin looping. In particular, we uncover the SE-driven upregulation of NAMPT, which promotes NAD+ and ATP metabolic reprogramming critical for filopodia formation and metastasis. Collectively, our study details the complex mechanistic link between TWEAK/Fn14 signalling and TNBC metastasis, which reveals several vulnerabilities which could be pursued for the targeted treatment of TNBC patients.

cancer biology↗

bioRxiv2021

PICASSO: Ultra-multiplexed fluorescence imaging of biomolecules through single-round imaging and blind source unmixing

Ultra-multiplexed fluorescence imaging of biomolecules is essential to studying heterogeneous biological systems. However, this is challenging due to fluorophores spectral overlap and variation of the emission spectra. Here, we propose a strategy termed PICASSO, which enables more than 15-colour multiplexed imaging of thick tissue slices through a single imaging process and blind unmixing without reference spectra measurement. We show that PICASSO can be used to achieve a high multiplexing capability in diverse applications, such as 3D protein imaging, expansion microscopy, tissue clearing, imaging of clinical specimens, and cyclic immunofluorescence imaging. PICASSO only requires an equal number of images as the number of fluorophores, enabling such a high level of multiplexed imaging even with bandpass filter-based microscopy. As such, PICASSO would be a useful tool for the study of cancer, the immune system, and the brain, as well as for the diagnosis of cancer, as it enables ultra-multiplexed imaging of diverse specimens with minimum instrumental requirements and experimental processes.

neuroscience↗