CCN1 (Cellular Communication Network Factor 1)

Findings corroborate the idea of a mechanistic role for YAP1 in neuroblastoma adrenergic to mesenchymal reprogramming and therapy resistance. The YAP1-mediated plastic switch towards a mesenchymal expression state in neuroblastoma cells may provide the molecular basis for novel therapeutic avenues.

These findings provide novel insights into the mechanisms underlying chemotherapy-induced drug resistance in CRC and highlight the release of Cyr61 by CRC cells as a potential therapeutic target for overcoming OXA resistance in CRC.

Using CRISPR/Cas9-mediated knockout and rescue experiments in EOC cell lines, we demonstrate that MED12 deficiency significantly enhances sensitivity to ferroptosis inducers (RSL3 and Erastin), as evidenced by reduced IC50 values...Pharmacological inhibition of YAP with verteporfin or siRNA-mediated TEAD1 knockdown reverses ferroptosis sensitivity in MED12-deficient cells, confirming pathway specificity. These findings establish MED12 as a modulator of the YAP-TEAD1-ferroptosis axis and suggest that targeting this pathway could overcome chemoresistance in MED12-deficient EOC. Our work provides a mechanistic foundation for exploiting ferroptosis induction as a therapeutic strategy in ovarian cancer.

Furthermore, our study demonstrated for the first time that Nab-PTX inhibits angiogenesis via the CYR61/Integrin αvβ3 signaling pathway. These findings elucidate a potential anti-angiogenesis mechanism of Nab-PTX and highlight CYR61's promise as a therapeutic target in human breast cancer.

Molecular docking predicted strong interactions with several clinically relevant compounds, including antioxidants and senolytics, with Metformin showing the highest affinity (SwissDock AC score: -200.26)...This study is the first to computationally demonstrate the druggability of CCN1 and to identify candidate small molecules with the potential to modulate its activity in aging- and disease-related contexts. Our findings provide both mechanistic insight and a scalable workflow for rapid screening of CCN1-targeted therapeutics.

In this study, we investigated the anti-inflammatory and anti-invasive properties of 1,3,6-tri-O-galloyl-α-D-glucose (αTGG), the α-anomer of βTGG from Terminalia chebula, in comparison with pharmacological Hippo pathway inhibitors IAG933, VT107, and GNE7883...Importantly, αTGG and VT107 also significantly attenuated ConA-induced activation of proMMP-2 to MMP-2 and reduced the expression of multiple pro-inflammatory mediators, including COX2, CCL22, CCR2, CCR4, CXCL10, CXCL12, CXCR1, FASLG, IFNG, IL13, and IL17A. These findings underscore the dual anti-inflammatory and anti-invasive actions of αTGG, positioning it as a promising candidate for targeting inflammation-driven GBM progression through modulation of Hippo pathway activity.

In vivo, HK03 treatment markedly reduced metastatic burden in a B16-F10 lung metastasis model. These findings suggest that honokiol derivatives, particularly HK03, represent potential lead compounds for targeting the YAP-TEAD axis in melanoma therapy.

Mechanistically, OTUD5 functioned as a deubiquitinase, removing the K48 ubiquitin chain from YAP and maintaining protein stability. Functionally, OTUD5 knockdown markedly attenuated HSCs-induced HT-29 cell proliferation and invasion in vitro and tumor growth in vivo. Our results highlight the critical role of OTUD5/YAP feedback loop in stiffness-induced HSC activation, offering a potential therapeutic target for colorectal liver metastasis.

The YAP inhibitor Verteporfin blunted MELK-driven PASMC proliferation and migration, underscoring the central role of YAP/TAZ signaling. Finally, in vivo pharmacological inhibition of MELK by OTS167 markedly reduced right ventricular systolic pressure, hypertrophy, and pulmonary vascular remodeling in Su/H mice, confirming the therapeutic relevance of MELK targeting in PAH. Collectively, these findings identify MELK as a novel regulator of PASMC pathobiology in PAH and suggest that it may represent a potential therapeutic target.

EBF3 transcriptionally activates ACADL and blocks the Hippo/YAP pathway to inhibit BC progression.

In vivo, OPN-9652 delays the onset of acquired resistance to BRAF inhibitors and MEK inhibitors from minimal residual disease. Thus, TAZ-TEAD activity plays an important role in melanoma drug tolerance and the development of acquired resistance.