SMAD2 (SMAD Family Member 2)

We also identify SMAD-based transcriptional and epigenetic signatures with prognostic and predictive utility across multiple tumor types. This integrative review provides a unified framework for understanding the SMAD signaling network as both a mechanistic driver and therapeutic vulnerability in cancer.

Collectively, these results underscore the potential of PRP as a therapeutic candidate for disrupting the intricate interactions within the PDAC TME. Further research and clinical investigations are necessary to validate the translational potential of PRP as an adjunct therapy for PDAC.

As an underlying mechanism, TGF-β signaling was critical for MMP14-mediated necroptosis activation, with SMAD Family Member 2 (SMAD2) directly binding to the Receptor-Interacting Protein 1 (RIP1) promoter. Altogether, MMP14 promotes a range of malignant behaviors and orchestrates a TGF-β-dependent necroptosis heterogeneity landscape in GBM; therefore, targeting MMP14-TGF-β signaling could be a novel strategy to counteract therapeutic resistance in GBM.

CD248 participates in HG-induced EMT of renal tubular epithelial cells and renal fibrosis by regulating TGF-β1/Smads pathway, and VER and NBIF are two potential natural drugs which targets it to ameliorate DN.

However, whether GCs directly affects lung cancer progression remains unclear. This study focused on the effects of dexamethasone (DEX) on the proliferation and migration of lung cancer cells as well as the related potential mechanisms using EdU, CCK8, Transwell, Wound healing, TCGA database, HPA database, qPCR and Western blotting...DEX can inhibits A549 cell proliferation and migration through suppressing Smad2/3 activation independent of GR. DEX inhibited the proliferation and migration of lung cancer cells by suppressing Smad2/3 activation, providing a theoretical basis and experimental data for clinical practice.

Short-term DBP exposure (mice: 10-50 mg/kg/day; HcerEpic cells: 100-400 μM) induced cervical injury/oxidative stress, suppressed NRF2, and activated MAPK/NF-κB; N-acetylcysteine (NAC) supplementation mitigated damages. Long-term exposure to environmentally relevant DBP concentrations (10-7 M) promoted HcerEpic cell malignant transformation (e.g., enhanced proliferation, migration, invasion, epithelial-mesenchymal transition) via activation of the TGF-β/Smad2/3 and MAPK pathways, with in vivo tumorigenicity validated in nude mice. In conclusion, our findings not only elucidate the molecular mechanisms underlying DBP-induced cervical injury and malignant transformation, but also provide theoretical evidence for evaluating the health risks of phthalates (PAEs) and guiding prevention strategies for environmental pollutant-related female reproductive malignancies.

Additionally, TB activated immune-related pathways via ERK/MAPK signaling and upregulated genes such as SMAD2, SMAD3, and JUN. TB functions as an HSP90 inhibitor with dual anticancer and immunomodulatory properties in Estrogen Receptor-Positive (ER+) breast cancer cells. These findings suggest that TB represents a promising scaffold for the development of multi-targeted breast cancer therapies.

Taken together, experimental and computational evidence supports a dual-mechanistic model in which 4d promotes muscle proliferation and regeneration by (1) activating the MasR-PI3K/AKT/mTOR axis and (2) inhibiting the ACVR1/2A-SMAD pathway, counteracting the action of myostatin. These findings position compound 4d as a promising therapeutic candidate against muscle wasting disorders, including cancer-related cachexia, by inducing a robust and multifactorial anabolic response.

Our findings provide evidence for HA-CD44/RHAMM as a potential therapeutic target in ORKP and subsequent prevention of chronic kidney disease. While previous studies have implicated CD44 and RHAMM in renal disease and fibrosis, our work for the first time provides an integrated analysis of both receptors in the context of ORKP.

We identify NPY-NPY1R-TGFβ crosstalk as a novel mechanism enabling OSCC to exploit neural signals for PNI, highlighting a promising therapeutic target to block neural invasion and improve patient outcomes.

Mechanistically, cisplatin-induced CaMKII phosphorylation activated the Smad2/3 signalling cascade, whereas KN93 treatment suppressed this pathway, reducing fibrogenic responses. Collectively, these findings identify CaMKII as a key regulator of renal fibrosis in cisplatin-induced CKD and suggest that targeting CaMKII may represent a promising therapeutic strategy to mitigate long-term nephrotoxicity in patients receiving cisplatin chemotherapy.

These comprehensive findings demonstrate that ADAMTS1 gene expression is under the direct transcriptional control of SMAD factors in Hep3B cells, showing strong induction by both SMAD2/4 and SMAD3/4 complexes. This study provides the first mechanistic evidence for this direct regulation, significantly enhancing the understanding of how the TGF-β signaling axis controls ADAMTS1 expression. This insight is highly relevant to its pathological functions in angiogenesis, tissue remodeling, and cancer progression.