Biology subjects

Chiou, A.

Publications and source records attributed to Chiou, A..

3 recordsLinked to original sources

bioRxiv2022

Biofunctional matrix models reveal mineral-dependent mechanoregulation of bone metastatic breast cancer

Bone metastasis is a leading cause of breast cancer-related deaths and often initiated by tumor cell dissemination to osteogenic niches. During new bone formation, osteoblasts first deposit osteoid, the collagen I-rich, unmineralized component of bone ECM, within which carbonated hydroxyapatite nanoparticles subsequently form. However, it remains elusive how bone matrix mineralization dictates tumor cell phenotype due in part to the lack of relevant model systems. Using biofunctional, collagen I-based bone matrix models with physiological, intrafibrillar mineralization, we show that mineralization inhibits proliferation, while inducing a stem-like phenotype in tumor cells. These changes were due to reduced mechanosignaling contradicting the conventional assumption that increased rigidity caused by mineralization stimulates metastatic progression. Our findings are translationally relevant as the presence of mineral reduced tumor growth in vivo and upregulated a gene signature that correlated with decreased patient mortality. Our results could help explain why decreased bone mineral density increases the risk for bone metastasis in patients and highlight that bone metastasis models should integrate organic and inorganic matrix components in a manner that mimics physiological mineralization.

bioengineering↗

bioRxiv2021

Reconstructing co-dependent cellular crosstalk in lung adenocarcinoma using REMI

Cellular crosstalk in tissue microenvironments is fundamental to normal and pathological biological processes. Global assessment of cell-cell interactions (CCI) is not yet technically feasible, but computational efforts to reconstruct these interactions have been proposed. Current computational approaches that identify CCI often make the simplifying assumption that pairwise interactions are independent of one another, which can lead to reduced accuracy. We present REMI (REgularized Microenvironment Interactome), a graph-based algorithm that predicts ligand-receptor (LR) interactions by accounting for LR dependencies on high-dimensional, small sample size datasets. We apply REMI to reconstruct the human lung adenocarcinoma (LUAD) interactome from a bulk flow-sorted RNA-seq dataset, then leverage single-cell transcriptomics data to increase its resolution and identify LR prognostic signatures. We experimentally confirmed colocalization of CTGF:LRP6 as an interaction predicted to be associated with LUAD progression. Our work presents a novel way to reconstruct interactomes and a new approach to identify clinically-relevant cell-cell interactions.

bioinformatics↗

bioRxiv2020

TGF-beta/Activin ligand Myoglianin couples muscle growth to the initiation of metamorphosis

Although the mechanisms that control growth are now well understood, the mechanism by which animals assess their body size remains one of the great puzzles in biology. The final larval instar of holometabolous insects, after which growth stops and metamorphosis begins, is specified by a threshold size. We investigated the mechanism of threshold size assessment in the tobacco hornworm, Manduca sexta. The threshold size was found to change depending on the amount of exposure to poor nutrient conditions whereas hypoxia treatment consistently led to a lower threshold size. Under these various conditions, the mass of the muscles plus integuments was correlated with the threshold size. Furthermore, the expression of myoglianin (myo) increased at the threshold size in both M. sexta and Tribolium castaneum. Knockdown of myo in T. castaneum led to larvae that underwent supernumerary larval molts and stayed in the larval stage permanently even after passing the threshold size. We propose that increasing levels of Myo produced by the growing tissues allow larvae to assess their body size and trigger metamorphosis at the threshold size.

developmental biology↗