Tumor Invasion Research Articles

Lack of ST2 aggravates glioma invasiveness, vascular abnormality and immune suppression

Abstract Background Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, characterized by aggressive growth and a dismal prognosis. Interleukin-33 (IL-33) and its receptor ST2 have emerged as regulators of glioma growth, but their exact function in tumorigenesis have not been deciphered. Indeed, previous studies on IL-33 in cancer have yielded somewhat opposing results as to whether it is pro- or anti-tumorigenic. Methods IL-33 expression was assessed in a GBM tissue microarray and public databases. As in vivo models we used orthotopic xenografts of patient-derived GBM cells, and syngenic models with grafted mouse glioma cells. Results We analyzed the role for IL-33 and its receptor ST2 in non-malignant cells of the glioma microenvironment and find that IL-33 levels are increased in cells surrounding the tumor. Protein complexes of IL-33 and ST2 are mainly found outside of the tumor core. The IL-33-producing cells consist primarily of oligodendrocytes. To determine the function for IL-33 in the tumor microenvironment, we used mice lacking the ST2 receptor. When glioma cells were grafted to ST2-deficient mouse brains, the resulting tumors exhibit a more invasive growth pattern, and are associated with poorer survival, compared to wild-type mice. Tumors in ST2-deficient hosts are more invasive, with increased expression of extracellular matrix remodeling enzymes and enhanced tumor angiogenesis. Furthermore, the absence of ST2 leads to a more immunosuppressive environment. Conclusions Our findings reveal that glia-derived IL-33 and its receptor ST2 participates in modulating tumor invasiveness, tumor vasculature and immunosuppression in glioma.

Principles of Surgical Treatment of Soft Tissue Sarcomas

Soft tissue sarcoma (STS) is a group of highly heterogeneous tumors of mesenchymal origin that have variable primary site locations and clinical behavior. Despite the broad diversity of STS, the standard of care involves surgical resection with or without radiation therapy (RT) to control local recurrence and systemic treatment in select cases. The complexities of STS require a critical understanding of the preoperative work-up process, surgical treatment, and postoperative management. Advanced imaging plays a vital role in the characterization of the soft tissue mass, preoperative biopsy planning, and disease staging. Surgical treatment prioritizes wide resection with negative margins, supported by newer margin classification systems for better prognosis. Further, advancements in surgical technique have enabled limb-salvage surgery to largely replace amputation in the management of these tumors. Additional surgical considerations, such as nerve preservation, vascular reconstruction, and complex tissue closure, further highlight the complexity of STS management. Lastly, postoperative follow-up is critical for the early detection of local or distant recurrences. For complex cases, such as unplanned excisions or invasive tumors, strategies like re-resection may be beneficial. Ongoing research into imaging, chemotherapy, and targeted therapies will further refine management strategies, especially in complex and recurrent cases. This review highlights the essential aspects of STS surgical management and underscores the need for coordinated, multidisciplinary care to enhance both survival and quality of life for affected patients.

Metastatic Status and Dissection Effect of Regional/Extraregional Lymph Nodes in Japanese Patients with Squamous Cell Carcinoma of the Anal Canal: A Multicenter Retrospective Cohort Study.

Squamous cell carcinoma of the anal canal (SCCA) is a rare condition. Standard treatment includes chemoradiotherapy, with surgical treatment reserved for limited cases. In the future, the decrease in surgical frequency makes it more difficult to pathologically assess the depth of tumor invasion and lymph node status; therefore, those studies based on relatively recent surgical cases may offer valuable insights into diagnosing and treating SCCA. This multicenter, retrospective cohort study evaluated 435 patients with SCCA in Japan, of which 84 underwent surgical lymph node dissection. The correlation of regional/extraregional lymph node metastasis with T-primary tumor category/depth of tumor invasion, and the index of estimated benefit from lymph node dissection (IEBLD) was evaluated histopathologically. Primary tumor progression was associated with metastasis and recurrence of the inguinal node and further inferior mesenteric trunk/root node metastasis, an extraregional lymph node. The IEBLD for the inferior mesenteric trunk/root node was 6.9, which was higher than 4.0 IEBLD of the lateral lymph nodes classified as the regional lymph nodes. The assessment of the primary tumor involvement can predict metastases of the inguinal node and inferior mesenteric trunk/root node and recurrence of the inguinal node. Although the UICC TNM Classification considered the inferior mesenteric trunk/root nodes as extraregional lymph nodes, actively targeting them with the treatment can improve the prognosis.

Selective resection of the medial wall of the cavernous sinus in pituitary surgery: results of a prospective single center analysis.

Pituitary adenomas, despite their histologically benign nature, can severely impact patients' quality of life due to hormone hypersecretion. Invasion of the medial wall of the cavernous sinus (MWCS) by these tumors complicates surgical outcomes, lowering biochemical remission rates and increasing recurrence. This study aims to share our institutional experience with the selective resection of the MWCS in endoscopic pituitary surgery. This prospective study included patients diagnosed with pituitary adenomas who underwent endoscopic endonasal surgery at Mayo Clinic, Jacksonville. Inclusion criteria encompassed confirmed pituitary adenomas, selective MWCS resection, and availability of histopathological data. Patient demographics, tumor characteristics, surgical outcomes, and postoperative complications were analyzed using descriptive statistics. Twenty-six cases met the inclusion criteria. Functional adenomas and macroadenomas constituted 80.8% of cases. Recurrent adenomas represented 19.2% of cases. Tumor invasion of the MWCS was confirmed in 76.9% of cases and patients with acromegaly had the highest rate of confirmed invasion of the MW (88.8%). Initial disease control was achieved in 88.5% of the patients, and disease remission at last follow up was observed in those with acromegaly, Cushing's disease and prolactinomas in 87.5%, 83.3% and 66.6% of cases, respectively. Complete resection was achieved in 5/5 nonfunctioning adenomas. There were no carotid injuries, cranial deficits or fatalities observed. Resection of the MWCS is an effective strategy for improving surgical outcomes in pituitary adenomas with potential invasion into this area, especially in patients with functional and/or recurrent adenomas. The procedure demonstrates a positive balance of efficacy and safety, when performed by teams with high level of experience in endoscopic skull base surgery and in selected patients.

Mitochondrial DNA copy number alterations: Key players in the complexity of glioblastoma (Review).

Renowned as a highly invasive and lethal tumor derived from neural stem cells in the central nervous system, glioblastoma (GBM) exhibits substantial histopathological variation and genomic complexity, which drive its rapid progression and therapeutic resistance. Alterations in mitochondrial DNA (mtDNA) copy number (CN) serve a crucial role in GBM development and progression, affecting various aspects of tumor biology, including energy production, oxidative stress regulation and cellular adaptability. Fluctuations in mtDNA levels, whether elevated or diminished, can impair mitochondrial function, potentially disrupting oxidative phosphorylation and amplifying reactive oxygen species generation, thereby fueling tumor growth and influencing treatment responses. Understanding the mechanisms of mtDNA‑CN variations, and their interplay with genetic and environmental elements in the tumor microenvironment, is essential for advancing diagnostic and therapeutic strategies. Targeting mtDNA alterations could strengthen treatment efficacy, mitigate resistance and ultimately enhance the prognosis of patients with this aggressive brain tumor. The present review summarizes the existing literature on mtDNA alterations, specifically emphasizing variations in mtDNA‑CN and their association with GBM by surveying articles published between 1996 and 2024, sourced from databases such as Scopus, PubMed and Google Scholar. In addition, the review provides a brief overview of mitochondrial genome architecture, knowledge regarding the regulation of mtDNA integrity and CN, and how mitochondria significantly impact GBM tumorigenesis. This review further presents information on therapeutic approaches for restoring mtDNA‑CN that contribute to optimized mitochondrial function and improved health outcomes.

Silencing superoxide dismutases (SOD1&SOD2) potentiates ROS-induced apoptosis in chordoma cells.

Chordoma, characterized as a slow growing yet locally invasive and destructive bone tumor mainly emerging in the sacrum and clivus, presents a unique challenge due to its rarity, hampering the development of effective treatment strategies. Comprehensive understanding of tumor biology is crucial to suggest novel treatment modalities. Reactive oxygen species (ROS), a family of chemically reactive and unstable oxygen derivatives, are controlled by an intracellular antioxidant system to maintain homeostasis. Higher doses of ROS levels have been associated with the oxidative stress-induced tumor cell death, highlighting the potential of fine-tuning ROS regulation as a target for cancer therapies. The association of ROS mechanism and chordoma remains to be elucidated. In this study, we investigated the effect of targeting the ROS mechanism in chordoma, focusing on superoxide dismutase 1 and superoxide dismutase 2. Two different chordoma datasets were used to assess oxidative stress-related genes. ROS levels and mitochondrial membrane potential (mtMP) in chordoma cells were measured. The gene expression levels of SOD1 and SOD2 in chordoma patients were also evaluated. SOD2 and SOD1 targeted siRNAs were used to silence gene expression in chordoma cells, and quantitative real-time PCR (qRT-PCR) was used to compare gene expression levels. Apoptotic cell populations were determined using flow cytometry. The levels of ROS and mtMP were increased in chordoma cell lines compared to healthy nucleus pulposus cells. The chordoma omics data showed induced levels of SOD2. Chordoma tissues also showed high levels of the SOD2 gene. Silencing SOD2 and combined silencing of SOD2 and SOD1 expression increased ROS levels or mtMP, and both induced apoptosis in chordoma cells. ROS imbalance plays a role in chordoma pathogenesis. SOD2 and SOD1 might be key enzymes in chordoma to modulate ROS levels, and inhibiting the SOD2 and SOD1 activity might be a potential therapeutic target for chordoma treatment.

Giant Odontogenic Myxoma of the Maxillary: A Rare Entity

Introduction: Maxillary odontogenic myxoma is a locally invasive benign mesenchymal tumor. The objective of this case observation was to discuss the difficulties related to the management of a case of giant maxillary odontogenic myxoma. Observation: This was a 32-year-old patient who consulted in the stomatology and maxillofacial surgery department of the CHU-CNOS Pr HT of Bamako for a swelling of the left hemiface evolving for 3 years with deterioration of the general condition. She has no particular medical or surgical history. On physical examination, there was a large swelling of the left hemiface measuring 35/21cm, hard and painless to palpation. There was also exophthalmos of the left eye, filling of the left nasal fossa, left suborbital hypoesthesia, and ipsilateral submandibular adenopathy. A maxillofacial CT scan and operability assessment were performed. After intense renutrition, surgical excision was performed under general anesthesia with a primary tracheotomy. Histological examination of the surgical specimen concluded that it was an odontogenic myxoma. The outcome was favorable, there was no recurrence after 12 months. Conclusion: Odontogenic myxoma is a benign tumor with slow progression and can be locally invasive, making surgical management difficult.

Clinico-Pathological Significance of Tumor Infiltrating Immune Cells in Oral Squamous Cell Carcinoma-Hope or Hype?

To correlate between immunohistochemical expression of tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), and natural killer (NK) cells with the AJCC 8th edition TNM staging system and other disease-modifying clinico-pathological variables. The representative histology sections of tumor invasive margin (IM) and tumor core (TC) were selected according to the International Immuno-Oncology Biomarker Working Group and were subjected to immunohistochemistry with antibodies for TILs (CD3, CD8, FOXP3), NK Cells (CD57), TAMs (CD68, CD163) and pan-leukocyte marker (CD45). Histo-immuno-density-intensity (HIDI) scoring was calculated as a product of the proportion and intensity of staining. Ordinal-ordinal and continuous-ordinal variables were correlated using Kendall's tau-b (τb), and binary-ordinal variables were correlated using Rank-Biserial (rrb) statistics. A total of 111 patients were included in the study. None of the clinical and pathological parameters showed a strong correlation with any of the immune infiltrates including TNM staging. We hypothesize an independent activity of tumor immunology in the disease prognosis. CTRI/2020/07/026335.

Tumour-Associated Macrophages in Oral Squamous Cell Carcinoma.

Tumour-associated macrophages (TAMs) are crucial in the progression and treatment response of oral squamous cell carcinoma (OSCC). TAMs infiltrate OSCC, adopting an M2-like phenotype that promotes tumour growth, metastasis and immune suppression. The current narrative review explored the roles of TAMs in OSCC, focusing on their impact on the tumour microenvironment, invasion, metastasis, angiogenesis, immunosuppression and potential therapeutic targeting. A comprehensive analysis of the current literature on TAMs in OSCC was conducted. Specifically, we evaluated the biological functions of TAMs, their interactions within the tumour microenvironment, and their influence on disease progression and treatment outcomes. TAMs contribute to OSCC progression by secreting cytokines, such as IL-10 and TGF-β, that inhibit effector immune cells. They facilitate angiogenesis, extracellular matrix remodelling and the epithelial-mesenchymal transition, which are essential for tumour invasion and metastasis. TAMs support cancer stem cells and recruit regulatory T cells and myeloid-derived suppressor cells, enhancing resistance to therapies. Their presence correlates with advanced OSCC stages, lymph node metastasis and poor prognosis. TAMs regulate OSCC progression and therapy resistance. Reprogramming them to an M1-like phenotype or depleting them enhances treatments. Understanding TAM-OSCC interactions is crucial for developing interventions against their tumour-promoting functions and restoring anti-tumour immunity.

Angelicin Inhibits NSCLC Tumor Growth via the Inhibition of Cancer-Associated Fibroblasts.

This study aimed to investigate the effect of angelicin on the NSCLC tumor growth. Accumulating evidence shows that cancer-associated fibroblasts (CAFs) play an important role in tumor progression and metastasis, making CAFs an increasingly attractive target for therapeutic intervention. Targeted therapies against CAFs have been considered to have the potential to significantly improve cancer treatment outcomes, overcome resistance, and improve immune evasion. Angelicin (Ang), an active ingredient isolated from the Chinese herbal medicine Psoralea corylifolia Linn., has been reported to inhibit tumor progression. Due to its natural origin, angelicin has good clinical safety and low toxicity. Further clinical studies and exploration of its role as a CAF inhibitor in difficult-to-treat tumors like as NSCLC are expected to offer up a new channel for cancer treatment. Furthermore, angelicin's low cost and good biocompatibility make it have important application potential in cancer combination therapy, especially when used in combination with traditional therapies such as chemotherapy and immunotherapy, which may significantly improve treatment outcomes and reduce side effects. However, the mechanism of its anti-tumor effect remains poorly defined. The aim of this study was to investigate whether ANG modulates CAF activity to inhibit NSCLC progression. NIH3T3 cells are a mouse fibroblast cell line, and the use of NIH3T3 cells as a model for CAFs is mainly due to their natural fibroblast phenotype, ease of culture, good response to stimuli, and ability to simulate the functions of fibroblasts in the tumor microenvironment. NIH3T3 was treated with TGF-β (4ug/ml) and H2O2 (10μM). A conditioned medium was used to study the effect of Ang on tumor growth, invasion, and migration by regulating CAFs.Ang concentrations were set at 12.5, 25, and 50μM for cell cycle experiments and 0, 20, and 40μM for cell migration and invasion experiments. Subcutaneous tumors were established by mixing LLC and NIH3T3 cells to observe the effect of Ang on tumor progression and microenvironment. Fibroblast activity during Ang intervention was monitored by fluorescence-labeled FAPI-04 and 18F-labeled FAPI-04. The molecular pharmacological mechanism of Ang was investigated by RNA sequencing and network pharmacology. The result showed that Ang significantly inhibited TGF-β and H2O2-induced NIH3T3 transformation, as evidenced by reduced expression of markers such as FAPα and α-SMA. Ang inhibited proliferation, invasion and migration of LLC cells induced by CAFs-conditioned medium. In vivo Experiments showed that Ang greatly inhibited tumor growth in Lewis's lung cancer caused by CAFs. Molecular pharmacological analysis showed that Ang could modulate CAFs activity through multiple targets. These data indicate that Ang has a great potential to reduce CAF activity, interfere with the tumor microenvironment, and inhibit tumor growth. However, these findings still need to be further validated, especially considering the heterogeneity of CAFs, the differences between in vitro and in vivo models, and potential side effects. Ang reduced the growth, invasion, and migration of lung cancer by inactive CAFs. This provides a rationale for tumor microenvironment-based treatment of lung cancer and clinical translation of Ang. As a potential anti-cancer drug, Ang has shown significant effects in inhibiting cancer-related fibroblasts (CAFs) and disrupting the tumor microenvironment. However, there are still challenges in translating these findings into clinical treatments, such as heterogeneity of the tumor microenvironment, differences in patient responses, and side effects. Therefore, future research should focus on exploring personalized treatment strategies, evaluating the clinical safety and effectiveness of the drug, and delving deeper into the molecular mechanisms and target sites of Ang.

Oridonin Suppresses the Malignant Progression of Lung Cancer by Targeting S100A11.

Lung cancer (LC) is the second most lethal cancer and efficient treatments are missing. Our understanding of the underlying pathogenic mechanisms remains limited. Oridonin is a compound extracted from the Chinese herb Rabdosia rubescens with anticancer properties. Nevertheless, its effects on LC and the underlying mechanisms remain unknown. In the current research, A549 and Hcc1833 cells were treated with different doses of oridonin, and cell proliferation and migration were detected using CCK8, EdU, Transwell, and wound healing assays. A subcutaneous tumor and caudal vein metastasis model was generated to verify the inhibitory effects of oridonin on Hcc1833 tumor growth and metastasis in vivo. Proteomics analyses then were performed to examine the regulatory mechanism. LiP-SMap combined with microscale thermophoresis and molecular docking analyses were used to validate the relationship between oridonin and S100A11. Data showed that oridonin suppressed cell proliferation and migration depending on dose and suppressed tumor growth and invasion. LiP-SMap and molecular docking analyses confirmed that oridonin interacted with the Asn-53 residue of S100A11, which inhibited the activation of oridonin. S100A11 overexpression reversed the inhibitory effects of oridonin on cell proliferation and migration. In conclusion, the data indicate that oridonin suppresses LC malignant progression by targeting S100A11.

ALB inhibits tumor cell proliferation and invasion by regulating immune microenvironment and endoplasmic reticulum stress in clear cell renal cell carcinoma.

The aim of this work is to identify putative hub genes for the advancement of clear cell renal cell carcinoma (ccRCC) and determine the fundamental mechanisms. We employed multiple bioinformatics techniques to screen hub genes. Key hub gene expression levels in ccRCC were assessed. A plethora of functional experiments were carried out to explore the biological role of hub gene. Based on genome-wide association studies, a Mendelian randomization research was conducted to ascertain the causative relationship between albumin (ALB) and ccRCC. ALB was low expression in ccRCC tissues and cell lines. It was an independent predictor of progression-free survival following treatment and the overall survival of ccRCC patients. ALB overexpression exhibited the reverse effects of ALB knockdown, which increased cell proliferation, migration, and invasion while inhibiting cell death. Similarly, ALB overexpression inhibited the growth of ccRCC tumors in vivo. Consistent with functional enrichment analysis, ALB overexpression activates the endoplasmic reticulum stress (ERS) in vitro and vivo. The Mendelian randomization showed ALB was associated with the risk of ccRCC. Additionally, ALB was causally associated with γδT cells infiltrates in ccRCC. ALB plays an important effect in ccRCC via activation of the ERS and regulating immune microenvironment.

Cancer‐Derived Extracellular Vesicle ITGB2 Promotes the Progression of Triple‐Negative Breast Cancer via the Activation of Cancer‐Associated Fibroblasts

AbstractBreast cancer is the most prevalent cancer and a leading cause of death among women globally, posing a significant public health challenge. Triple‐negative breast cancer (TNBC), an aggressive subtype accounting for 15–20% of all breast cancers, lacks targeted therapies due to the absence of hormone receptors and HER2, resulting in poor prognosis and high recurrence rates. This study investigates the role of cancer‐derived extracellular vesicle (EV) integrin beta‐2 (ITGB2) in TNBC progression. These findings reveal that ITGB2 is significantly overexpressed in TNBC tissues and serum EVs, correlating with advanced tumor stages and poor patient survival. ITGB2 enhances TNBC progression by activating cancer‐associated fibroblasts (CAFs) within the tumor microenvironment, promoting tumor growth, migration, and invasion. Mechanistic studies demonstrate that EV ITGB2 facilitates CAF activation, driving tumor‐stroma interactions that support TNBC progression. These results highlight ITGB2 as a potential biomarker and therapeutic target in TNBC, emphasizing the need for novel interventions to combat this challenging breast cancer subtype.

Prognostic Implications of Decorin, E-Cadherin and EGFR Expression in Inflammatory and Non-Inflammatory Canine Mammary Carcinomas.

Inflammatory mammary carcinoma (IMC) is the most aggressive variant of invasive mammary tumours in dogs and in women. Decorin is an extracellular matrix molecule whose expression can be reduced or absent in various human cancers, which is associated with a poor prognosis. E-cadherin is a cell adhesion protein whose expression is reduced in several neoplasms. However, it is overexpressed in inflammatory breast cancers of women. EGFR is also associated with cancer development and is commonly overexpressed in aggressive neoplasms. This study aimed to characterise the expressions of Decorin, E-cadherin, and EGFR in canine inflammatory and non-inflammatory mammary carcinomas (IMC and non-IMC) and to evaluate their expression levels as prognostic indicators for survival and occurrence of metastases. Thirty-three IMC and 43 non-IMC cases were analysed retrospectively and submitted to immunohistochemical analysis. The reactions were quantified in five high-power field images from areas of the highest intensity and frequency of immunostaining (hot spots). We found significantly lower expression of Decorin and higher of E-cadherin and EGFR in canine IMCs. Patients with tumours that exhibited Decorin expression in less than 26.35% of epithelial cells had shorter survival (p = 0.0410) and a higher occurrence of distant metastases (p = 0.0115). E-cadherin is overexpressed in canine IMCs (p < 0.0001), similar to what occurs in women, reinforcing that dogs can be used as a study model for human IMC. EGFR overexpression in canine IMCs (p = 0.0322) provides evidence for potential targeted therapy with tyrosine kinase inhibitors.

Decoding the Role of Kinesin Superfamily Proteins in Glioma Progression.

Glioma is a highly aggressive and invasive brain tumor with limited treatment options, highlighting the need for novel therapeutic approaches. Kinesin superfamily proteins (KIFs) are a diverse group of motor proteins that play essential roles in cellular processes such as mitosis, intracellular transport, and signal transduction, all of which are crucial for tumorigenesis. This review focuses on the multifaceted role of KIFs in glioma, examining their clinical relevance, contribution to tumor progression, and potential as therapeutic targets. We discuss how KIFs influence key aspects of glioma biology, including cell proliferation, invasion, migration, and metastasis. Furthermore, we explore the regulation of the cell cycle and critical signaling pathways associated with glioma, such as PI3K-Akt, Wnt/β-catenin, and Hedgehog signaling by KIFs. The review also addresses the emerging interplay between KIFs and non-coding RNAs, including circular RNAs (circRNAs) and microRNAs (miRNAs), in glioma progression. Finally, we examine current therapeutic strategies targeting KIFs, including immunotherapy, chemotherapy, and small-molecule inhibitors, and their potential to improve treatment outcomes for glioma patients. By synthesizing these insights, this review underscores the significance of KIFs in glioma pathogenesis and their promise as novel therapeutic targets in the fight against glioma.

Invasive stratified mucin-producing carcinoma of the cervix: A case report and review of the literature

ABSTRACT Invasive stratified mucin-producing carcinoma (ISMC) is a rare, recently described subtype of HPV-associated cervical adenocarcinoma. It shows varied morphological patterns, making it difficult to diagnose, especially the mixed forms. A 57-year-old female, P7L7, presented with postmenopausal bleeding for the past five months. On per-vaginal examination, a friable cervical growth was noted. Microscopic examination of the cervical biopsy showed an invasive tumor composed of nests of stratified columnar cells with peripheral palisading and a variable amount of (alcian blue-positive) intracytoplasmic mucin. Another component of the tumor showed sheets and nests of undifferentiated tumor cells. IHC on both components showed diffuse positivity for P16, PAX8, and keratin 7. Based on these findings, a diagnosis of ISMC was made. Awareness of the morphological features and ancillary stain results of ISMC can aid in picking up the diagnosis in a small biopsy. These findings have prognostic value, as most cases of ISMC behave aggressively.

Glut-1 exerts anti-tumor activity in glioma by regulating AKT / mTOR signaling pathway

Objective Glioma is a common tumor in neurosurgery. Glut-1 is the main carrier of glucose uptake by cells and can provide energy through the glycolytic pathway. However, the role and related mechanisms of Glut-1 in glioma have not yet been elucidated. Methods Real time PCR and Western blot were done to assess Glut-1 level in glioma tumor tissues and adjacent tissues. Glioma U87 cells were separated into control group; Glut-1 negative control (NC group); and Glut-1 siRNA group followed by analysis of Glut-1 expression, cell proliferation by MTT assay, cell invasion, cell apoptosis and cycle by flow cytometry and AKT / mTOR signaling proteins level by Western blot. Results Glut-1 expression was significantly increased in the tissues of glioma patients (P &lt; 0.05) compared to adjacent tissues and its level was related to tumor size, pathological grade and survival. Down-regulating the expression of Glut-1 can significantly inhibit tumor cell proliferation and invasion, increase apoptosis and induce G0 phase of cell cycle arrest, and inhibit the expression of AKT / mTOR signaling proteins phosphorylation (P &lt; 0.05). Conclusions Glut-1 level in glioma tissues is significantly increased, which is related to the pathological features. Down-regulating Glut-1 can inhibit glioma by regulating the AKT / mTOR signaling pathway.

MT1JP: A Pivotal Tumor-Suppressing LncRNA and its Role in Cancer Progression and Therapeutic Potential.

Metallothionein 1J pseudogene (MT1JP) is a long non-coding RNA (lncRNA) that functions as a tumor suppressor in various malignancies. Reduced MT1JP expression is associated with increased tumor proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and treatment resistance in nine cancers, such as gastric cancer, intrahepatic cholangiocarcinoma, hepatocellular carcinoma, and breast cancer. Mechanistically, MT1JP acts as a competitive endogenous RNA (ceRNA) to regulate oncogenic microRNAs (miRNAs), including miR-92a-3p, miR-214-3p, and miR-24-3p. This regulation restores tumor suppressor genes, such as FBXW7, RUNX3, and PTEN, thereby disrupting oncogenic pathways, including PI3K/AKT, Wnt/βcatenin, and p53, promoting apoptosis, and inhibiting tumor progression. Clinically, MT1JP expression correlates with tumor grade, differentiation, TNM stage, lymph node metastasis, and patient prognosis, suggesting its potential as a diagnostic and prognostic biomarker. Furthermore, its therapeutic potential in RNA-based treatments has attracted significant attention. Despite these findings, questions remain regarding its role in epigenetic regulation, transcriptional control, and RNA delivery. This review explores the molecular mechanisms underlying MT1JP, highlighting its clinical relevance and potential as a therapeutic target. Future research should focus on elucidating its role in epigenetic regulation, overcoming challenges in therapeutic delivery, and validating its utility as a biomarker for different cancers. MT1JP holds promise for advancing precision oncology by providing innovative approaches for cancer diagnosis and treatment.

MARVELD1 Promotes the Invasiveness in Pancreatic Adenocarcinoma through the Activation of Epithelial-to-Mesenchymal Transition.

MARVEL domain-containing 1 (MARVELD1) has been implicated in the progression of several cancers, but its role in pancreatic adenocarcinoma (PAAD) remains poorly understood. RNA-seq data from the TCGA-PAAD and GTEx-Pancreas cohorts were analyzed to assess MARVELD1 expression. Stable MARVELD1 knockdown and overexpression were conducted in BxPC3 and PANC-1 cells. Cell viability, proliferation, migration, and invasion were evaluated using functional assays, and western blotting was employed to examine EMT-associated protein levels, including Vimentin, MMP2, MMP9, and E-cadherin. Differentially expressed genes (DEGs) between MARVELD1-high and MARVELD1-low groups were identified, and pathway enrichment analyses were performed. We observed a significant increase of MARVELD1 in PAAD patient samples, with elevated MARVELD1 levels correlating with poor clinical survival. Knockdown of MARVELD1 in PAAD cells remarkably decreased cell proliferation and colony formation, while overexpression of MARVELD1 enhanced these properties. Moreover, simulated cell invasion and migration assay further suggested that MARVELD1 might contribute to PAAD cell aggressiveness. Mechanistically, MARVELD1 promoted tumor cell migration and invasion through the activation of Vimentin, MMP2, and MMP9 protein while suppressing E-cadherin. Bioinformatics analysis revealed that MARVELD1-high samples were enriched in EMT-related pathways, including TGF-β receptor signaling, actin cytoskeleton regulation, and cell adhesion. Taken together, our study highlights the roles of MARVELD1 in promoting tumor cell proliferation and invasion, suggesting its potential application as a prognostic and diagnostic biomarker for PAAD in the clinical context.

A Novel 167-Amino Acid Protein Encoded by CircPCSK6 Inhibits Intrahepatic Cholangiocarcinoma Progression via IKBα Ubiquitination.

Intrahepatic cholangiocarcinoma (ICC), a formidable challenge in oncology, demands innovative biomarkers and therapeutic targets. This research highlights the importance of the circular RNA (circRNA) circPCSK6 and its peptide derivative circPCSK6-167aa in ICC. CircPCSK6 is significantly downregulated in both ICC patients and mouse primary ICC models, and its lower expression is linked to adverse prognosis, highlighting its pivotal role in ICC pathogenesis. Functionally, this study elucidates the regulatory effect of circPCSK6-167aa on IκBα ubiquitination within the NF-κB pathway, which is mediated by its competitive binding to the E3 ligase RBBP6. This complex interaction leads to reduced activation of the NF-κB pathway, thereby curbing tumor cell proliferation, migration, invasion, stemness, and hepatic-lung metastasis in vivo. This groundbreaking discovery expands the understanding of circRNA-driven tumorigenesis through atypical signaling pathways. Additionally, this investigation identified EIF4A3 as a detrimental regulator of circPCSK6, exacerbating ICC malignancy. Importantly, by leveraging patient-derived xenograft (PDX), organoids, and organoid-derived PDX models, higher levels of circPCSK6-167aa enhance sensitivity to gemcitabine, indicating its potential to improve the effectiveness of chemotherapy. These insights emphasize the therapeutic promise of targeting circPCSK6-167aa, offering vital biological insights and clinical directions for developing cutting-edge therapeutic approaches, thus revealing innovative strategies and targets for future treatments.