Cancer Cell International最新文献

Pancreatic cancer is known to be the most lethal cancer. Fewer new treatments are being developed for pancreatic cancer as compared to other cancers. The bioactive lipid S1P, which is mainly regulated by sphingosine kinase 1 (SK1) and sphingosine kinase 2 (SK2) enzymes, plays significant roles in pancreatic cancer initiation and exacerbation. S1P controls many signaling pathways to modulate the progression of pancreatic cancer through the G-coupled receptor S1PR1-5. Several papers reporting amelioration of pancreatic cancer via modulation of S1P levels or downstream signaling pathways have previously been published. In this paper, for the first time, we have reviewed the results of previous studies to understand how S1P and its receptors contribute to the development of pancreatic cancer, and whether S1P can be a therapeutic target. In addition, we have also reviewed papers dealing with the effects of SK1 and SK2, which are kinases that regulate the level of S1P, on the pathogenesis of pancreatic cancer. We have also listed available drugs that particularly focus on S1P, S1PRs, SK1, and SK2 for the treatment of pancreatic cancer. Through this review, we would like to suggest that the SK/S1P/S1PR signaling system can be an important target for treating pancreatic cancer, where a new treatment target is desperately warranted.

Lung cancer has the highest incidence and mortality rates worldwide and is the primary cause of cancer-related death. Despite the rapid development of diagnostic methods and targeted drugs in recent years, many lung cancer patients do not benefit from effective therapies. The emergence of drug resistance has led to a reduction in the therapeutic effectiveness of targeted drugs, highlighting a crucial need to explore novel therapeutic targets. Many studies have found that epigenetic plays an important role in the occurrence of lung cancer. This review describes the biological function of epigenetic RNA modifications, such as m6A, m5C, m7G, and m1A, and recent advancements in their role in the development, progression, and prognosis of lung cancer. This review aims to provide new guidance for the treatment of lung cancer.

Background: Pancreatic cancer is a malignant tumor of the digestive tract with a high mortality rate. Erianin has antitumor activity, but the regulatory targets and mechanism of action in pancreatic cancer are unclear. The objective of this study was to evaluate the anti-pancreatic cancer activity of Erianin and explore its underlying mechanisms.

Methods: A network pharmacology approach was used to investigate the mechanism of action of Erianin in pancreatic cancer cells. Cell proliferation was analyzed using CCK8, colony-formation, and EdU proliferation assays. Cell migration was evaluated through wound healing and transwell assays, as well as determination of the protein expression levels of EMT markers and β-catenin. Apoptosis and the cell cycle were measured using flow cytometry and JC-1 staining, respectively. The protein expression levels of p-Rb, CyclinB1, P21, Cleaved-PARP, and Cleaved-Caspase3 were assessed using western blotting. RNA sequencing (RNA-seq) and bioinformatics analyses were performed to elucidate the mechanism underlying the action of Erianin in pancreatic cancer. Western blotting was used to examine the expression levels of key proteins in the AKT, JNK, and p38 MAPK signaling pathways. Molecular docking and CETSA were used to test hypotheses. The tumor-suppressive ability of Erianin in vivo was assessed using a tumor-bearing assay in nude mice.

Results: Network pharmacology revealed that Erianin inhibited pancreatic cancer through multiple pathways. Erianin significantly inhibited pancreatic cancer cell proliferation and migration while promoting intracellular ROS and inducing apoptosis. Mechanistically, Erianin inhibited pancreatic cancer cell proliferation by regulating the AKT/FOXO1 and ASK1/JNK/p38 MAPK signaling pathways. In vivo experiments showed that Erianin inhibited subcutaneous tumor growth and promoted tumor tissue apoptosis in nude mice.

Conclusions: The component-target-pathway network revealed that Erianin exerted anti-cancer effects through multiple components, targets, and pathways. Erianin inhibited the proliferation and migration of pancreatic cancer cells and induced apoptosis through the AKT/FOXO1 and ASK1/JNK/p38 MAPK signaling pathways. These results indicate that Erianin is a promising agent for pancreatic cancer treatment.

Background: Hepatocellular carcinoma (HCC) is a global health concern. Due to late diagnosis and limited therapeutic strategies, HCC based mortality rate is exponentially increasing globally. Genetic predisposition is a non-avoidable intrinsic factor that could alter the genome sequence, ultimately leading to HCC. Protein kinase C eta (PKCη) is involved in key physiological roles, hence alteration in PKCη could aid in cancer progression. Research indicates association between non-synonymous (ns) SNPs and HCC onset. However, effect of nsSNP variants of PKCη on HCC development has not been explored yet. Hence, this study aimed to investigate the association between pathogenic nsSNPs of PKCη with HCC.

Methods: Non-synonymous (missense) variants of PKCη were obtained from Ensembl genome browser. These variants were filtered out to obtain pathogenic nsSNPs of PKCη. Genotyping of nsSNPs was done through Tetra ARMS PCR. For that, blood samples of 348 HCC patients and 337 controls were collected. The clinical factors that influence HCC were studied. Relative risk (RR) and Odds Ratio (OR) with 95% confidence interval was calculated by Chi-square test and P-value < 0.05 was deemed significant.

Results: Five nsSNP variants of PKCη including rs1162102190 (T/C), rs868127012 (G/T), rs750830348 (G/T), rs768619375 (T/C), and rs752329416 (T/C) were identified. The retrieved nsSNPs were frequently identified in HCC patients. However, rs752329416 T/C was significantly prevalent in patients having HCC family history. Moreover, all the variants were found in HCC patients manifesting the stage II than the advance stages of HCC.

Conclusion: This study can be utilized to identify potential genetic markers for early screening of HCC. Moreover, consideration of further clinical factors, and mechanistic approach would enhance the understanding that how alteration in nsSNPs could impact the HCC onset.

Purpose: Heparan sulfate proteoglycans (HSPGs) are complex molecules found on the cell membrane and within the extracellular matrix, increasingly recognized for their role in tumor progression. This study aimed to investigate the involvement of Heparan sulfate proteoglycan 2 (HSPG2) in the progression of bladder cancer.

Methods: We identified HSPG2 as a promoter of bladder tumor progression using single-cell RNA sequencing and transcriptome analysis of sequencing data from seven patient samples obtained from the Gene Expression Omnibus (GEO) database (GSE135337). Transcript profiles of 28 normal tissues and 407 bladder tumor tissues were analyzed for HSPG2 expression and survival outcomes using the Sanger tools and cBioPortal databases. HSPG2-overexpressing T24 and Biu-87 cell lines were generated, and cell proliferation and migration were assessed using CCK-8 and Transwell assays. Western blotting and immunostaining were performed to evaluate the activation of Nidogen-1 (NID1)/protein kinase B (AKT) signaling. Mouse models with patient-derived tumor organoids (HSPG2^high and HSPG2^low) were established to assess anticancer effects.

Results: Our results demonstrated a marked upregulation of HSPG2 in malignant bladder tumors, which correlated significantly with poor patient prognosis. HSPG2 overexpression consistently enhanced bladder tumor cell proliferation and conferred chemotherapy resistance, as shown in both in vitro and in vivo experiments. Mechanistically, HSPG2 upregulated NID1 expression, leading to the activation of the AKT pro-survival signaling pathway and promoting sustained tumor growth in bladder cancer.

Conclusion: This study highlights the critical pro-tumor role of HSPG2/NID1/AKT signaling in bladder cancer and suggests its potential as a therapeutic target in clinical treatment.

Cancer remains a major global health challenge, with the persistence of cancer stem cells (CSCs) contributing to treatment resistance and relapse. Despite advancements in cancer therapy, targeting CSCs presents a significant hurdle. Non-thermal gas plasma, also known as CAP, represents an innovative cancer treatment. It has recently gained attention for its often found to be selective, immunogenic, and potent anti-cancer properties. CAP is composed of a collection of transient, high-energy, and physically and chemically active entities, such as reactive oxygen species (ROS). It is acknowledged that the latter are responsible for a major portion of biomedical CAP effects. The dynamic interplay of CAP-derived ROS and other components contributes to the unique and versatile properties of CAP, enabling it to interact with biological systems and elicit various therapeutic effects, including its potential in cancer treatment. While CAP has shown promise in various cancer types, its application against CSCs is relatively unexplored. This review assesses the potential of CAP as a therapeutic strategy for targeting CSCs, focusing on its ability to regulate cellular states and achieve redox homeostasis. This is done by providing an overview of CSC characteristics and demonstrating recent findings on CAP's efficacy in targeting these cells. By contributing insights into the unique attributes of CSCs and the potential of CAP, this work contributes to an advanced understanding of innovative oncology strategies.

Background: High-risk strains of HPV are known to cause cervical cancer. Multiple clinical studies have emphasized that smoking and drinking are critical risk factors for cervical cancer and its high-grade precursors. In this study, we investigated if smoking and/or drinking augment the molecular mechanisms of cervical carcinogenesis and defined a potential therapeutic approach for their attenuation.

Methods: The impact of benzo[a]pyrene (B[a]P) and/or ethanol (EtOH) exposure on cervical cancer cells was assessed by measuring changes in their cell migration and invasion characteristics. Expression of HPV16 E6/E7, NF-κB, cytokines, and inflammation mediators was determined using qRT-PCR, immunoblotting, ELISA, luciferase reporter assay, and confocal microscopy. Herein, we used curcumin (Cur), and PLGA nanoparticle formulation of curcumin (PLGA-Cur) and determined effectiveness of free Cur and PLGA-Cur formulation on smoking and drinking activated NF-κB/IL-6 mediated inflammatory signaling pathways using in vitro cervical cancer models.

Results: Treatments with B[a]P and/or EtOH altered the expression of HPV16 E6/E7 oncogenes and EMT markers in cervical cancer cells; it also enhanced migration and invasion. In addition, B[a]P and/or EtOH exposure promoted inflammation pathways through TNF-α and NF-κB signaling, leading to IL-6 upregulation and activation of VEGF. The molecular effects caused by B[a]P and/or EtOH exposure were effectively attenuated by curcumin (Cur)/PLGA-Cur treatment.

Conclusions: These data suggest a molecular link between smoking, drinking, and HPV infectivity in cervical carcinogenesis. In addition, attenuation of these effects by treatment with Cur/PLGA-Cur treatment, implies the role of curcumin in cervical cancer prevention and treatment.

Background: Immune checkpoint blockade (ICB) has been improving the patient outcome in multiple cancer types. However, not all patients respond to ICB. Biomarkers are needed for selecting appropriate patients to receive ICB. CD74 is an important chaperone that regulates antigen presentation for immune response. However, the relationship between CD74 expression and ICB response remains elusive.

Methods: The unified normalized pan-cancer dataset was downloaded from the UCSC database. Wilcoxon Rank Sum Rank Tests were used to analyze the expression differences between normal and tumor samples in each tumor type. Then, the prognostic value of CD74 was determined using univariable Cox proportional hazards regression analysis. The STRING database was utilized to construct the protein-protein interaction (PPI) network of CD74 and the signal pathways were analyzed as well. The correlation of CD74 expression with immune cells and immune regulating genes was investigated in the TIMER database. The TIDE framework was utilized to evaluate the relationship between CD74 expression and the response to immunotherapy. Moreover, the localization of CD74 in the tumor immune microenvironment was verified using multiplex immunohistochemistry. Clinically annotated samples from 38 patients with esophageal cancer treated with neoadjuvant chemotherapy combined with ICB were analyzed for CD74 expression using immunohistochemistry.

Results: In this study, we investigated the prognostic and predictive value of CD74 in different types of cancer. Compared with normal tissue, the expression of CD74 was higher in tumor tissue in various cancers. High expression of CD74 was associated with improved patient prognosis in the majority of cancers. CD74 and its interacting proteins were mainly enriched in the immune-related pathways. The expression of CD74 was significantly positively correlated with B cells, CD4 T-cells, CD8 T-cells, neutrophils, macrophages and dendritic cells. TIDE analysis showed that tumors with high CD74 expression may have better responses to immunotherapy and improved patient survival. In patients with esophageal cancer who had received ICB, higher intratumoral CD74 expression was associated with improved response to ICB.

Conclusions: The findings of this study suggest that the high expression of CD74 may be a potential predictive biomarker of response to ICB.

Background: Sp1, a transcription factor, regulates essential cellular processes and plays important tumorigenic roles across diverse cancers. However, comprehensive pan-cancer analyses of its expression and potential immunomodulatory roles remain unexplored.

Methods: Utilizing bioinformatics tools and public datasets, we examined the expression of Sp1 across normal tissues, tumors, and immune cells, and screened for pre- and post-transcriptional modifications, including genetic alterations, DNA methylation, and protein phosphorylation, affecting its expression or function. The association of Sp1 expression with immune cell infiltration, tumor mutational burden, and immune checkpoint signaling was also investigated. Single-cell transcriptome data was used to assess Sp1 expression in immune cells in gastric cancer (GC), and findings were corroborated using immunohistochemistry and multiplex immunofluorescence in an immunotherapy-treated patient cohort. The prognostic value of Sp1 in GC patients receiving immunotherapy was evaluated with Cox regression models.

Results: Elevated Sp1 levels were observed in various cancers compared to normal tissues, with notable prominence in GC. High Sp1 expression correlated with advanced stage, poor prognosis, elevated tumor mutational burden (TMB), and microsatellite instability (MSI) status, particularly in GC. Significant correlations between Sp1 levels and CD8+ T cell and the M1 phenotype of tumor-associated macrophages were further detected upon multiplex immunofluorescence in GC samples. Interestingly, we verified that GC patients with higher Sp1 levels exhibited improved response to immunotherapy. Moreover, Sp1 emerged as a prognostic and predictive biomarker for GC patients undergoing immunotherapy.

Conclusions: Our pan-cancer analysis sheds light on the multifaceted role of Sp1 in tumorigenesis and underscores its potential as a prognostic and predictive biomarker for patients with GC undergoing immunotherapy.