SMAD2 (SMAD Family Member 2)

These results also highlight the therapeutic potential of targeting stromal SMAD3/TIMP-1 in LUAD or microenvironmental stressors such as hypoxia and acidosis in LUSC. In addition, these findings provide a biological framework for understanding the histotype-dependent patterns of dissemination, immune evasion, and response to anti-angiogenic therapies in NSCLC.

Loss of LSD1 enzymatic activity or INSM1 knockout abrogated TAS1440 effects, defining its mode of action and chemoresistance. These findings support TAS1440 as a next-generation epigenetic therapy candidate for INSM1-high SCLC-A.

These effects were mediated through downregulation of the c-Jun N-terminal kinase/p65/c-Jun signaling pathway. In conclusion, these findings demonstrate that xaliproden confers reno-protective effects by mitigating renal tubular epithelial cell damage and improving renal function in DKD, suggesting its potential as a therapeutic option for DKD.

Nonetheless, the study has limitations, including reliance on a single cell line and the assessment of direct apoptosis only. These findings highlight a complex interplay between GAS5, CD20, rituximab, and cellular pathways, underscoring the significance of understanding these interactions to enhance cancer therapy outcomes.

It also inhibited the expression levels of p-STAT5, p-STAT3 and p-smad2/3 in BRCA cells. We identified four hub genes closely related to the prognosis of BRCA, and a risk model constructed by these four genes may be useful for risk stratification and prognosis evaluation in BRCA patients.

These findings suggest that CCL4 plays a critical role in AKI pathophysiology, particularly in regulating inflammatory and fibrotic processes through STAT3. Our results suggest that targeting CCL4 may provide a novel therapeutic approach to mitigate AKI and prevent its progression to chronic kidney disease.

We evaluated the antitumor effect of the combination therapy with osimertinib and either nintedanib (an indirect TGF-β inhibitor) or vactosertib (a specific TGF-β type I receptor kinase inhibitor). In conclusion, combination therapy with osimertinib and TGF-β inhibitors potentiates osimertinib-induced antitumor immunity. These findings highlight a novel therapeutic strategy for EGFR-mutated NSCLC and warrant further clinical investigation.

In contrast, SMAD4 and SMAD2 showed frequent loss-of-function-type alterations in GAS, including copy-number loss, but were not detected in LEGH. These findings provide insights into the genomic landscapes of LEGH and GAS and suggest potential molecular markers for this transition, which may inform future diagnostic and therapeutic research.

In this study, we utilized a lactate-deficient cell line created by the knockout of PKM2 to examine the effects of promoter-level histone H3 lysine 18 lactylation (H3K18la) on the regulation of the DNMT3A gene, which subsequently influences SMAD2 expression and modulates the TGF-β signaling pathway and cellular proliferation in breast cancer. Our findings elucidate a novel metabolic-epigenetic axis that cancer cells utilize to drive tumorigenesis.

Furthermore, SP1 degradation, SMAD activation, and their DNA binding patterns show the reciprocal role of p300 on SP1 and SMAD complexes. Altogether we have identified SMAD2/4 as an activator complex, p300 as a positive regulator, and uncovered a critical p300-SMAD-SP1 regulatory axis in GM2-synthase transcriptional regulation.

Mechanistically, COMP shifted transforming growth factor beta (TGFβ) signaling from canonical phosphorylated mothers against decapentaplegic homolog 2/3 (pSMAD2/3) activation toward pSMAD1/5, likely through its interaction with PMEPA1. This study suggests the COMP-PMEPA1 axis as a new driver of EMT in breast cancer models.

In addition, PAQR3 overexpression reduced TGF-b1, p-Smad3, and p-Smad2 (P < 0.001), while increasing Smad3 and Smad2, indicating suppression of the TGF-b pathway. These findings suggest that PAQR3 inhibits metastasis and induces ferroptosis in HCC through TGF-b pathway regulation.