Biology subjects

Wong, B. M.

Publications and source records attributed to Wong, B. M..

2 recordsLinked to original sources

bioRxiv2026

The Extracellular Matrix Regulates Invasion in Fusion-Negative Rhabdomyosarcoma via YAP-PIEZO1 Signaling Axis

BackgroundFusion-negative rhabdomyosarcoma (FNRMS) represents the most prevalent subtype of rhabdomyosarcoma, the most common pediatric soft tissue sarcoma. Although its invasion is a leading cause of recurrence and poor prognosis, its underlying mechanism remains unclear. We investigated how extracellular matrix (ECM) density regulates FNRMS progression via mechano-transduction. MethodsWe used three-dimensional spheroid invasion assays with RD and SMS-CTR cells embedded in varying collagen concentrations. Mechanistic insights were gained through immunofluorescence, ChIP-seq re-analysis, Fluo-4 calcium live cell imaging, and pharmacological inhibition of the YAP-PIEZO1 axis. ResultsHigh ECM density significantly enhanced invasive spreading, correlating with increased YAP nuclear localization. YAP overexpression was sufficient to promote invasion, while its inhibition attenuated the matrix-enhanced phenotype. We identified PIEZO1 as a direct transcriptional target of the YAP. High ECM density stimulated PIEZO1-dependent calcium influx, which was required for invasion. Furthermore, elevated PIEZO1 expression was significantly associated with poorer overall survival in FNRMS patients. Targeting YAP or ROCK signaling effectively suppressed both calcium flux and invasion. ConclusionsOur findings establish a YAP-PIEZO1 axis linking ECM density to FNRMS invasion. This mechanosensitive pathway represents a potential therapeutic vulnerability in aggressive FNRMS. Simple SummaryFusion-negative rhabdomyosarcoma (FNRMS) is the prevalent subtype of rhabdomyosarcoma, the most common pediatric soft tissue sarcoma. Its invasion often leads to recurrence and poor prognosis. This study investigates how the density of the extracellular matrix (ECM), surrounding cancer cells in the tissue, influences FNRMS invasion. We found that high ECM density activates the protein YAP, which directly triggers the expression of the mechanical sensor PIEZO1. This sensor allows calcium to enter the cells, providing a signal that facilitates invasion. Pharmacological inhibition of this axis successfully reduced the invasive potential, highlighting a novel therapeutic vulnerability for FNRMS patients.

cancer biology↗

bioRxiv2019

Resting networks and personality predict attack speed in social spiders

Groups of social predators capture large prey items collectively, and their social interaction patterns may impact how quickly they can respond to time-sensitive predation opportunities. We investigated whether various organizational levels of resting interactions (individual, sub-group, group), observed at different intervals leading up to a collective prey attack, impacted the predation speed of colonies of the social spider Stegodyphus dumicola. We found that in adult spiders overall group connectivity (average degree) increased group attack speed. However, this effect was detected only immediately before the predation event; connectivity two and four days before prey capture had little impact on the collective dynamics. Significantly, lower social proximity of the groups boldest individual to other group members (closeness centrality) immediately prior and two days before prey capture was associated with faster attack speeds. These results suggest that for adult spiders, the long-lasting effects of the boldest individual on the groups attack dynamics are mediated by its role in the social network, and not only by its boldness. This suggests that behavioural traits and social network relationships should be considered together when defining keystone individuals in some contexts. By contrast, for subadult spiders, while the group maximum boldness was negatively correlated with latency to attack, no significant resting network predictors of latency to attack were found. Thus, separate behavioural mechanisms might play distinctive roles in determining collective outcomes at different developmental stages, timescales, and levels of social organization.\n\nSignificance statementCertain animals in a group, such as leaders, may have a more important role than other group members in determining their collective behavior. Often these individuals are defined by their behavioral attributes, for example, being bolder than others. We show that in social spiders both the behavioral traits of the influential individual, and its interactions with other group members, shape its role in affecting how quickly the group collectively attacks prey.

animal behavior and cognition↗