Macroautophagy/autophagy is a stress-responsive lysosomal catabolic pathway that promotes cellular homeostasis and tumor cell survival, but its role in breast cancer progression and metastasis remains unclear. Here, we show that a brain-specific serine/threonine protein kinase, BRSK2, a marker of aggressive metastatic disease in breast cancer patients, is crucial in regulating autophagy. BRSK2 is overexpressed in aggressive cancer and is associated with reduced disease-specific survival. BRSK2 also regulates basal autophagy and activates AKT, STAT3, and NF-κB-mediated cancer cell survival pathways. In addition, BRSK2 overexpression increases the levels of inflammatory cytokines and chemokines in breast cancer cells. Downregulation of BRSK2 using specific siRNAs or the BRSK2 kinase small-molecule inhibitor GW296115 markedly reduced nutrient-deprivation stress-mediated autophagy, cell growth, and metastatic potential, and enhanced breast cancer cell apoptosis. Endogenous BRSK2 is associated with the Vps34-class III PI3K-Beclin-1-ATG14 autophagy signaling complexes that could protect cancer cells from nutrient-deprivation stress. Our findings demonstrate the key role of the BRSK2-mediated protective autophagy and cell growth and survival under nutrient deprivation stress via survival signals, e.g., PI3K/AKT or STAT3-NF-kB, in aggressive breast cancer cells.

Understanding the characteristics of the tumor microenvironment (TME) associated with aggressive prostate cancer (PCa) is essential for accurate diagnosis and treatment. We interrogated spatially resolved multi-omics data to find molecular stratifiers of aggressive PCa. We report an aggressive prostate cancer (APC) gene expression signature predictive of increased risk of relapse and metastasis in a cohort of 1,588 patients. Further, we present a chemokine-enriched-gland (CEG) signature specific to non-cancerous prostatic glands from patients with aggressive cancer. The CEG signature is characterized by upregulated expression of pro-inflammatory chemokines, club-like cell enrichment, and immune cell infiltration of surrounding stroma. The activity of both signatures is correlated with reduced citrate and zinc levels and loss of normal prostate secretory gland functions. In summary we report that an increased inflammatory status linked to chemokine production, club-like cell enrichment, and metabolic changes in normal-appearing prostatic glands is associated with the subsequent development of aggressive PCa.

The dataset (Elsafty_Reports_of_Myeloid_Neoplasms_2024) consists of 14,441 comprehensive clinicopathologic correlations (CPCs) for myeloid neoplasms (MN) with corresponding laboratory results. Specialized online platform utilizing these laboratory results automatically generated the diagnostic and prognostic CPCs. These results include complete blood counts (CBC), peripheral blood smear (PBS) findings, blast/promyelocyte count with dysplasia screening by flow cytometry, and molecular results by NGS/PCR. Two Hematopathologists, who performed the CBC and PBS review, collected their 10,794 real-world reports of cases served in Egypt with molecular studies performed in the USA and Europe. These newly-diagnosed cases included 243 chronic myeloid leukemia (CML) cases with 257 mutations/aberrations; 4,567 non-CML MN cases with 7,883 Tiers I/II mutations/aberrations, amino acid changes, and allele frequencies; and 5,984 benign/inconclusive cases with negative NGS for myeloid mutations/aberrations in 66 DNA/RNA genes. Additionally, there are 3,647 CPCs with synthetic genomics simulating all new/follow-up CML cases and complex/rare non-CML MN cases. Stringent validation by 51 international professors/consultants/specialists from multiple medical centres confirmed 100% medical and clerical accuracy, referencing the WHO 5th edition and relevant esteemed publications.

Esophageal squamous cell carcinoma (ESCC) is associated with variable clinical outcomes, even among tumours with similar characteristics, complicating treatment. Here, we identify acetyl-CoA carboxylase 1 (ACC1), a key lipogenic enzyme, as a factor influencing this variability. Specifically, ACC1 knockdown in ESCC cells induces histone acetylation, activating c-Fos and C-X-C motif chemokine ligand 8 (CXCL8) transcription, which in turn promotes epithelial-mesenchymal transition (EMT) and enhances migration and invasion via CXCL8-C-X-C motif chemokine receptor 1/2 (CXCR1/2)-mediated PI3K/AKT and MEK/ERK signalling. Additionally, ACC1 knockdown stimulates neutrophil recruitment and neutrophil extracellular trap (NET) formation through CXCL8-dependent paracrine signalling, further enhancing tumour cell migration and invasion. In ESCC xenografts, ACC1 knockdown increases neutrophil infiltration and NET formation, accelerating metastasis. Clinically, low ACC1 expression and high CXCL8 levels are linked to poor prognosis in patients with ESCC, while NET formation further correlates with reduced survival. These findings highlight the ACC1-CXCL8-NET axis as a potential therapeutic target and prognostic marker in ESCC.

Circular RNAs (circRNAs) have emerged as critical regulators in cancer progression. This study aimed to investigate the role of circ_0003266 in bladder cancer (BCa) and elucidate its underlying molecular mechanisms. The expression levels of circ_0003266, miR-503-5p, and SMAD7 in BCa tissues and cell lines were determined using bioinformatics analysis, clinical data, and quantitative real-time PCR (qPCR). Cellular phenotypes were evaluated through proliferation, migration, and apoptosis assays. RNA pull-down and luciferase reporter assays were conducted to validate the molecular interactions among circ_0003266, miR-503-5p, and SMAD7. The involvement of the TGF-β signaling pathway was assessed by Western blotting and co-immunoprecipitation (Co-IP) analysis. Circ_0003266 expression was significantly downregulated in BCa tissues and cell lines, and its low expression was clinically correlated with larger tumor size and advanced disease stage, including poor differentiation and higher TNM classification. Upregulation of circ_0003266 inhibited BCa cell proliferation and migration while promoting apoptosis. Mechanistic analyses revealed that miR-503-5p is a direct target of circ_0003266, and that circ_0003266-mediated regulation of miR-503-5p subsequently modulates SMAD7 expression. SMAD7, a well-established inhibitor of the TGF-β pathway, was shown to mediate the tumor-suppressive effects of circ_0003266. In vivo experiments confirmed that overexpression of circ_0003266 attenuated tumor growth and suppressed TGF-β signaling activity. Our findings demonstrate that circ_0003266 exerts tumor-suppressive functions in BCa by modulating the miR-503-5p/SMAD7/TGF-β axis, highlighting its potential as a novel therapeutic target for bladder cancer intervention.

Basement membrane-related genes (BMRGs) play a crucial function in the progression of various malignancies. This study aimed to explore the relationship between BMRGs and colon cancer.

Whole-genome doubling (WGD) is a macro-evolutionary event that is both prevalent and prognostically significant in human cancers, particularly in high-grade serous ovarian carcinoma (HGSOC). Historically, WGD has been viewed as a consequence of widespread genomic instability, but recent advancements in single-cell sequencing (sc-seq) have reframed its role as a central, dynamic driver of tumor evolution. This review summarizes cutting-edge findings, demonstrating how WGD acts as a catalyst for a distinct evolutionary trajectory characterized by the rapid accumulation of chromosomal losses and the selection of highly adaptable clones. A key finding is the resolution of a biological paradox: WGD-driven chromosomal instability, which should provoke an immune response, is instead correlated with a profoundly immunosuppressive phenotype via the repression of key innate immune pathways. Finally, this review discusses the clinical implications of these discoveries, highlighting WGD's potential as a predictive biomarker and a source of unique therapeutic vulnerabilities, paving the way for targeted strategies in advanced HGSOC.

Glutathione (GSH) plays a central role in multiple physiological processes, including the maintenance of intracellular redox homeostasis and the detoxification of xenobiotics. While previous studies have linked GSH metabolism to the pathogenesis and treatment of hepatocellular carcinoma (HCC), systematic analysis of the expression profiles of GSH metabolism-related genes in HCC and their consistent correlation with patient prognosis remains insufficiently addressed.

In Martinique, there is an unmet need in EC management. Although the incidence rate is similar to that in mainland France, the mortality rate is higher, potentially due to the over-incidence of high-grade tumors. Recently, we reported CCNE1 amplification in 70% of these tumors which have a poor prognosis. This alteration has been observed in non-endometrioid subtypes of African American women. To elucidate the over-incidence of poor prognosis EC in Martinique, we aim to describe molecular profiles especially CCNE1 amplification of a cohort of all patient diagnosed between January 2023 and June 2024.

This study aimed to assess the contributions of metabolism, perfusion, and diffusion kurtosis imaging (DKI) to the diagnosis and prognostic prediction of H3K27-altered diffuse midline gliomas (DMGs).

SMAD-specific E3 ubiquitin protein ligase 1 (Smurf1) is involved in various biological processes through targeting specific proteins for ubiquitin-dependent degradation. Emerging evidence has shown that Smurf1 functions as an oncogene in many types of human tumours, including gastric cancer (GC). We aimed to investigate the role of Smurf1 in regulating GC progression and reveal its underlying mechanism. Smurf1 expression was analyzed using two publicly available datasets. Additionally, it was assayed in 29 pairs of GC tissues and para-cancerous tissues using quantitative reverse transcriptase PCR (qRT-PCR). The biological roles of Smurf1 in GC cells were assessed in vitro and in a mouse xenograft model. The results showed that Smurf1 levels were significantly up-regulated in GC tissues compared with normal tissues, and high Smurf1 expression was significantly correlated with worse disease-free survival (DFS). Forced expression of Smurf1 accelerated AGS cell growth, proliferation, and invasion in vitro and in vivo. Mechanistically, Smurf1 directly interacted with axis inhibition protein 2 (Axin2) and diminished the stability of the Axin2 protein by promoting its ubiquitination and subsequent degradation. As a result, Smurf1 promoted the activation of Wnt/β-catenin signaling. Importantly, IWR-1, a specific inhibitor of the Wnt pathway, effectively inhibited Smurf1-induced GC cell proliferation and invasion. These data suggest that upregulated Smurf1 facilitates GC progression through degrading Axin2 and activating Wnt/β-catenin signaling.

Accurate multicancer classification constitutes a cornerstone of modern oncology, offering critical insights into diagnosis, therapeutic decision-making, and prognostication. Numerous existing approaches, however, remain restricted to limited cancer types and typically encode genomic information into a single representational modality. The purpose of this study was to develop and evaluate a novel framework by integrating complementary, mutation-derived features to advance cancer classification.

Interleukin-1β (IL-1β) is a key inflammatory mediator in cancer. Its precursor, Pro-IL-1β, is conventionally considered inactive. Here we demonstrate that head and neck squamous cell carcinoma (HNSCC) cells exhibit significantly elevated Pro-IL-1β expression, driven by super-enhancer-mediated transcription of the IL1B gene. We show that intracellular Pro-IL-1β promotes tumor invasion and metastasis independent of IL-1β processing. Mechanistically, Pro-IL-1β binds RACK1 and inhibits its UBE2T-mediated ubiquitination, thereby stabilizing RACK1 and activating RhoA signaling to induce actin cytoskeleton remodeling and pseudopodia formation. Genetic inhibition of RACK1 abolishes Pro-IL-1β-induced metastasis. Clinically, RACK1 protein levels correlate with Pro-IL-1β expression in HNSCC specimens. Furthermore, we identify the natural compound Q3MG as a direct binder of Pro-IL-1β; it promotes lysosomal degradation of Pro-IL-1β and suppresses metastatic progression both in vitro and in vivo. Our study reveals a non-canonical, moonlighting function of Pro-IL-1β in tumor progression and highlights Q3MG as a promising therapeutic agent against metastatic cancer.

Diet and genetic risk are established risk factors for kidney cancer, but their interaction remains unclear. This study aims to systematically investigate the associations between various dietary patterns and kidney cancer risk, as well as to evaluate the combined effects of diet and genetic risk on kidney cancer risk.

Sterol-O acyltransferase 1 (SOAT1) functions by converting cholesterol and acyl-CoA into cholesterol ester and CoA-SH. SOAT1 inhibition suppresses tumor growth. A recent study has shown that inhibiting cholesterol esterification in T cells using genetic manipulation or drug treatment of SOAT1 boosted the cytotoxicity of CD8+ T cells. To better understand the role of SOAT1 in the tumor immune microenvironment of ovarian cancer (OC) and to optimize combined immunotherapy strategies, we examined the effect of SOAT1 manipulation and drug inhibition in OC cells on CD8+ T cell-mediated immune response in vitro.

Lung cancer remains one of the leading causes of mortality globally. For patients with epidermal growth factor receptor (EGFR) -mutated lung adenocarcinoma who develop resistance to first-line EGFR-tyrosine kinase inhibitors (EGFR-TKIs), subsequent treatments typically involve a regimen that includes pemetrexed and platinum. However, the progression-free survival (PFS) achieved with this approach is limited to 4-5 months. There is an urgent need for effective and safe adjuvant therapies. Preliminary research suggests that Chinese herbal medicine (CHM) granules may extend PFS and improve quality of life (QoL), potentially offering a therapeutic strategy for advanced non-small-cell lung cancer (NSCLC). A rigorous, randomized clinical trial is warranted to confirm these findings. The aim of this study is to evaluate the efficacy and safety of CHM granules in combination with chemotherapy for patients with EGFR-mutated advanced lung adenocarcinoma following resistance to first-line EGFR-TKIs.

The most prevalent cancer in pediatric is acute lymphoblastic leukemia (ALL). The multidrug resistance gene (MDR1) encodes the membrane transport protein P-glycoprotein (P-gp), which acts as an efflux pump. Interleukin 18 (IL18), an 18-kilodalton cytokine, plays a complex role in cancer, exhibiting both anti-cancer and pro-cancer properties. This study aims to investigate the association between polymorphisms in the MDR1 gene (G2677T, rs2032582) and IL18 gene variants (607C > A, rs1946518 and - 137G > C, rs187238) and their potential role in susceptibility to pediatric ALL in an Egyptian population. We hypothesize that specific polymorphisms in MDR1 and IL18 genes are significantly associated with an increased risk of developing pediatric ALL, and that these genetic variants may serve as potential biomarkers for early detection and prognosis.

Colorectal cancer (CRC) is a prevalent malignancy with the efficacy of current treatments limited. Nitidine chloride (NC), a natural alkaloid, exhibits antitumor potential, but its mechanism in CRC remains unclear.

The chromatin immunoprecipitation followed by sequencing (ChIP-seq) assay is an instrumental and accurate method for understanding chromatin dynamics in eukaryotic cells. It provides critical insights into the regulation of gene expression and enables identification of regulatory elements, patterns of histone modifications, and chromatin states in health and disease conditions. Although cell cultures are great models to study molecular mechanisms associated with pathologies, studying tissues provides a physiologically native environment that reflects the cellular heterogeneity and spatial organization that are missing in an in vitro model. Several ChIP-seq protocols have been published; however, performing ChIP-seq in tissues remains a challenge in many settings due to the heterogeneity of tissues, complexity of cell matrices, low input material and intricacy of chromatin fragmentation and handling. Here, we present an optimized ChIP-seq protocol for solid tissues, with a focus on colorectal cancer. In this article, we incorporate simplified and efficient procedures for tissue preparation, chromatin extraction, immunoprecipitation, and library construction. The refined protocols overcome common limitations related to tissue processing and allows for highly reproducible, sensitive, and scalable analysis of disease-relevant chromatin states in vivo. © 2025 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Frozen tissues preparation Basic Protocol 2: Chromatin immunoprecipitation from tissues Basic Protocol 3: Library construction for DNA sequencing Basic Protocol 4: DNA nanoballs preparation for the DNBSEQ-G99RS sequencing platform and data quality control.

Chen et al demonstrated that regulator of G protein signaling (RGS) 4 promotes gastric cancer (GC) progression by activating the focal adhesion kinase/phosphatidyl-inositol-3-kinase/protein kinase B pathway and inducing epithelial-mesenchymal transition. Although their multilevel approach integrating clinical data, functional assays, and xenograft models demonstrated a key role for RGS4 in GC pathogenesis, several limitations should be considered. The mechanism of the RGS4-focal adhesion kinase interaction remains unclear, specifically whether it involves direct binding or intermediaries. The clinical analysis of 90 patients lacks stratification by GC subtypes or immune features, potentially limiting generalizability. Furthermore, fully validating RGS4's oncogenic role requires additional studies, including functional assays in chemotherapy-resistant and metastatic cell lines, metastasis models including orthotopic implantation and tail vein injection, and comparison with other RGS family members. Addressing these via targeted mechanistic studies and expanded clinical validation could strengthen RGS4's potential as a therapeutic target in GC.