Objective: Endometrial cancer (EC) remains a significant clinical challenge, particularly for patients with advanced or recurrent disease. This study aims to investigate the effects of Sanguinarine Chloride (S.C), a natural benzophenanthridine alkaloid with broad anti-tumor properties, on EC cell growth and invasion, and to elucidate its underlying molecular mechanisms. Methods: S.C’s effects on EC cell viability, proliferation, invasion, and apoptosis were evaluated using CCK-8, EdU, colony formation, 3D matrigel drop assay, FACS and Western blotting (WB). To evaluate its effects on ferroptosis, malondialdehyde (MDA) assay kits, DCFH-DA and the C11 BODIPY581/591 probe, were employed. The molecular mechanisms through which S.C regulates FTO-ACSL4 axis were investigated using plasmid transfection and WB. Additionally, a mouse xenograft model derived from EC cells was established to evaluate the in vivo effects of S.C and its molecular mechanisms, utilizing hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC) and WB. Results: S.C significantly inhibited EC cell growth and invasion. It induced cell death primarily through ferroptosis, as inhibitors (Ferrostatin-1, Deferoxamine) reversed this effect. S.C downregulated the RNA demethylase FTO, leading to increased ACSL4 expression, enhanced lipid peroxidation, suppression of the NRF2-GPX4 axis, and activated NCOA4-mediated ferritinophagy. Knocking down or pharmacologically inhibiting ACSL4 reduced S.C-induced ferroptosis. Furthermore, in a murine xenograft model, S.C significantly suppressed tumor growth, which was associated with consistent alterations in these ferroptosis-related markers in vivo. Conclusions: Our findings reveal that S.C triggers ferroptosis in EC via the novel FTO-ACSL4 axis, highlighting its potential as a therapeutic agent and identifying the FTO-ACSL4 pathway as a promising target for endometrial cancer treatment.

IGF2BP3-GP130-STAT3-WTAP loop promotes the malignant progression in glioblastoma.

Association of C5AR1 polymorphisms with increased gastric cancer risk: mechanistic insights and therapeutic implications targeting JAK/STAT pathway.

Introduction: The t(12;21)(p13;q22) is the most common chromosomal translocation in pediatric B cell precursor acute lymphoblastic leukemia (BCP-ALL), occurring in 5% of healthy newborns. This alteration generates the ETV6::RUNX1 (E::R) fusion gene, encoding an aberrant transcription factor that is insufficient to cause leukemia directly, but establishes a clinically silent pre-leukemic progenitor not yet fully characterized. We previously showed that E::R expression in the murine pro-B BaF3 cells caused the slowdown of cell cycle progression and increased phospho-histone H2AX levels, both features of Oncogene Induced Senescence (OIS).Methods. We explored whether E::R induces OIS in immature hematopoietic cells to uncover therapeutic targets for pre-leukemia. We used two E::R+ pre-leukemic models: an inducible BaF3 Pro-B cell system and Sca1-E::R transgenic mice, where E::R is expressed in immature Lin−Sca1+ cells.Results. We observed that E::R caused a senescence-like phenotype in BaF3 cells, characterized by altered morphology, increased β-galactosidase activity (% SA β-Gal positive cells: ctr = 8.05 ± 10,61; E::R = 50.02 ± 9.95, p<0.0001), elevated reactive oxygen species (ROS) (fold change of CM-H2DCFDA MFI, E::R versus ctr = 1.42 ± 0.41, p<0.001), and Senescence-Associated Secretory Phenotype (SASP) factor secretion. It dysregulated genes within the p53 pathway, including senescence-related genes, causing the accumulation of p53 protein and alteration in its post-translational modifications. In E::R positive cells, while p53-mediated cell cycle arrest occurred, apoptosis was impaired, providing a survival advantage under genotoxic stress mediated by etoposide (% annexin V+ ctr versus E::R cells: 0.5 μg/ml etoposide = 70 ± 6.6 versus 51 ± 6.7, p<0.01; 0.75 μg/ml etoposide = 76 ± 4.9 versus 64 ± 9.4, p=0.014). Multiple therapeutic approaches targeting these vulnerabilities were tested. Senolytics SSK1 and piperlongumine selectively eliminated E::R+ cells by exploiting elevated β-gal activity and ROS levels, respectively. TM5441 leveraged caspase-3 inhibitor PAI-1 upregulation to induce apoptosis. Furthermore, using Sca1-E::R transgenic mice, we validated E::R-induced OIS in the pre-leukemic Lin-Sca1+ immature population by observing an increased proportion of cells in G0 phase (% G0 cells: ctr = 59.34 ± 12.74; E::R = 73.19 ± 6.841, p = 0.0263), and enhanced SA β-Gal activity compared to WT mice (SA β-Gal MFI: ctr = 1941 ± 939.8; E::R = 2764 ± 1108, p = 0.03). We also observed reduced pre-B colony formation after SSK1 treatment (Ratio E::R pre-B colonies treated versus untreated: 1.6 pM SSK1 = 0.63 ± 0.11, p<0.01; 8 pM SSK1 = 0.61 ± 0.07, p < 0.01).Conclusions. These findings demonstrate E::R’s dual role in inducing OIS and conferring apoptosis resistance, highlighting the potential of senescence-targeted therapies to prevent leukemia progression and relapse in E::R carriers.

Di-(2-ethylhexyl) terephthalate promotes breast cancer progression: Multi-omics integrated experimental validation.

FAM83A promotes the progression of lung squamous cell carcinoma by inducing the epithelial-mesenchymal transition and inhibiting apoptosis via ERK pathway.

Ginsenoside Rh2 and luteolin synergistically induce cellular senescence to suppress hepatocellular carcinoma progression through oxidative stress-mediated mechanisms.

tRF-Ser-TGA-011 impedes gastric cancer progression by targeting the MAP3K13/JNK signaling cascade.

RNF6 activates JNK/c-JUN pathway in ovarian cancer by promoting K48-linked NME4 ubiquitination.

Ovarian cancer is a heterogeneous gynecologic malignancy, with most cases diagnosed at an advanced stage. Despite the availability of effective treatments such as surgery and platinum/taxane-based chemotherapy, advanced ovarian cancer frequently recurs, highlighting the need to investigate mechanisms of chemotherapy resistance. Delta-like non-canonical Notch ligand 1 (DLK1), a transmembrane protein of the EGF-like family, is aberrantly expressed in several cancers. Our previous study demonstrated that DLK1 promotes oncogenic behaviors and epithelial-mesenchymal transition in ovarian high-grade serous carcinoma. In this study, we observed a positive correlation between DLK1 and stemness markers CD44 and CD133 in human epithelial ovarian cancer using tissue microarray analysis. Overexpression of DLK1 by an adenovirus vector accelerated sphere-forming capability and upregulated CD44, CD133, and ABCG2 expression in human ovarian cancer cell lines. Conversely, DLK1 silencing by siRNA abolished the stimulatory effects on the stem cell-like properties and reduced CD44 and CD133 expression in ovarian cancer cells. Furthermore, DLK overexpression by an adenovirus vector enhanced colony formation and suppressed the cisplatin- and taxol-induced death in human ovarian cancer cells. Conversely, DLK1 siRNA reversed cell death and colony formation induced by these chemotherapeutic agents. Finally, we demonstrated that DLK1 regulates CD44, CD133, and ABCG2 expression through the Notch1/AKT/STAT3 signaling pathway, involving the phosphorylation and translocation of STAT3. Collectively, these results suggest that targeting DLK1 may represent a potential therapeutic strategy to improve outcomes in recurrent ovarian cancer following chemotherapy. © 2026 The Pathological Society of Great Britain and Ireland.

Imperatorin induces ferroptosis via mediating lipid peroxidation and SLC7A11/ACSL4/GPX4 signaling for inhibition and therapeutics of prostate cancer.

DLST mediates the malignant progression of osteosarcoma cells by regulating the p38 MAPK signaling pathway.

Marsdenia tenacissima extract potentiates the anti-lung cancer efficacy of gefitinib through dual regulation of the Wnt pathway and ferroptosis.

To investigate the role of ubiquitin-specific protease 7 (USP7) in thyroid cancer (TC) pathogenesis and sorafenib resistance. USP7 expression was compared in normal human thyroid cells and TC cells. The TC line with maximal differential USP7 expression was selected for further study. The functional interaction between USP7 and never in mitosis A (NIMA)-related kinase 2 (NEK2)/autophagy-related 5 (ATG5) was elucidated through a Pearson correlation coefficient analysis and co-immunoprecipitation assay. The half-inhibitory concentration (IC50) of sorafenib in resistant follicular thyroid (FTC) cells was determined following USP7 knockdown and ATG5 overexpression. Furthermore, the effects of USP7 knockdown and the autophagy inducer rapamycin (RAPA) on FTC cell function were assessed by colony formation and Transwell assays. The function of USP7 was validated in vivo using a xenograft mouse model, and tumor growth was assessed through gross examination and histopathological staining. High USP7 expression promoted the proliferation, migration, and invasion of FTC cells and was positively correlated with NEK2 and ATG5 levels. USP7 enhanced NEK2 stability via deubiquitination. Knocking down USP7 downregulated ATG5, and this effect was reversed by NEK2 overexpression. USP7 inhibition reduced the IC50 of sorafenib in FTC cells, which was reversed by ATG5 overexpression. USP7 knockdown attenuated FTC cell proliferation, migration, and invasion while increasing the apoptosis rate, and these effects were reversed by RAPA treatment. Knocking down USP7 suppressed the growth of TC xenografts in vivo, improved tumor tissue differentiation, and reduced the percentage of Ki-67-positive cells. USP7 promoted the progression of FTC and induced sorafenib resistance by enhancing NEK2/ATG5-mediated autophagy. This study provides novel insights and potential therapeutic strategies for FTC treatment and overcoming drug resistance.

Afatinib inhibits esophageal squamous cell carcinoma by regulating ferroptosis and NRF2 protein homeostasis.

Design, synthesis and biological evaluation of novel isoalantolactone-benzylamine derivatives leading to the discovery of a PARP1 inhibitor with selective cytotoxicity against MCF-7 breast cancer cells.

UBR5, a potential diagnostic and prognostic biomarker induces osteosarcoma progression.

MiR-146a-armed exosomes reverse immunosuppressive networks in NSCLC by dual-targeting of MYD88/STAT3 and PD-L1 axes.

Unraveling the secrets of UBE2S in endometrial cancer: Potential targets for diagnosis, prognostic assessment, and ferroptosis therapy.

Novel nanoparticle-combined therapy through EGFR and PD-L1 blockade: PFPR-siRNA-mediated suppressing NSCLC proliferation via PDT and enhanced antitumor immunity.