Tumor Progression Research Articles

The Indispensable Roles of GMDS and GMDS-AS1 in the Advancement of Cancer: Fucosylation, Signal Pathway and Molecular Pathogenesis.

Fucosylation is facilitated by converting GDP-mannose to GDP-4-keto-6-deoxymannose, which GDP-mannose 4,6-dehydratase, a crucial enzyme in the route, carries out. One of the most prevalent glycosylation alterations linked to cancer has reportedly been identified as fucosylation. There is mounting evidence that GMDS is intimately linked to the onset and spread of cancer. Furthermore, the significance of long-chain non-coding RNAs in the development and metastasis of cancer is becoming more well-recognized, and the regulatory mechanism of lncRNAs has emerged as a prominent area of study in the biological sciences. GMDS-AS1, an antisense RNA of GMDS, was discovered to have the potential to be an oncogene. We have acquired and analyzed relevant data to understand better how GMDS-AS1 and its lncRNA work physiologically and in tumorigenesis and progression. Additionally, we have looked into the possible effects of these molecules on cancer treatment approaches and patient outcomes. The physiological roles and putative processes of GMDS and lncRNA GMDS-AS1 throughout the development and progression of tumors have been assembled and examined. We also examined how these chemicals might affect patient prognosis and cancer therapy approaches. GMDS and GMDS-AS1 were determined to be research subjects by searching and gathering pertinent studies using the PubMed system. The analysis of these research articles demonstrated the close relationship between GMDS and GMDS-AS1 and tumorigenesis and the factors that influence them. GMDS plays a vital role in regulating fucosylation. The related antisense gene GMDS-AS1 affects the biological behaviors of cancer cells through multiple pathways, including the key processes of proliferation, migration, invasion, and apoptosis, providing potential biomarkers and therapeutic targets for cancer treatment and prognosis assessment.

ERK5 mediates pro-tumorigenic phenotype in non-small lung cancer cells induced by PGE2

Lung cancer is the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) constituting approximately 84 % of all lung cancer cases. The role of inflammation in the initiation and progression of NSCLC tumors has been the focus of extensive research. Among the various inflammatory mediators, prostaglandin E2 (PGE2) plays a pivotal role in promoting the aggressiveness of epithelial tumors through multiple mechanisms, including the stimulation of growth, evasion of apoptosis, invasion, and induction of angiogenesis. The Extracellular signal-Regulated Kinase 5 (ERK5), the last discovered member among conventional mitogen-activated protein kinases (MAPK), is implicated in cancer-associated inflammation. In this study, we explored whether ERK5 is involved in the process of tumorigenesis induced by PGE2. Using A549 and PC9 NSCLC cell lines, we found that PGE2 triggers the activation of ERK5 via the EP1 receptor. Moreover, both genetic and pharmacological inhibition of ERK5 reduced PGE2-induced proliferation, migration, invasion and stemness of A549 and PC9 cells, indicating that ERK5 plays a critical role in PGE2-induced tumorigenesis. In summary, our study underscores the pivotal role of the PGE2/EP1/ERK5 axis in driving the malignancy of NSCLC cells in vitro. Targeting this axis holds promise as a potential avenue for developing novel therapeutic strategies aimed at controlling the advancement of NSCLC.

Transcription factor ETS1‑mediated ECT2 expression promotes the malignant behavior of prostate cancer cells.

Prostate cancer remains the most prevalent malignancy diagnosed in men worldwide. Epithelial cell transforming sequence 2 (ECT2) is an oncogene involved in the progression of human tumors. The present study aimed to explore the involvement of ECT2 in prostate cancer and its participation in the malignant progression of prostate cancer. ECT2 expression in prostate cancer cell lines was examined via reverse transcription-quantitative PCR and western blotting. The effects of knockdown of ECT2 expression in PC-3 cells on cellular biological behaviors, including proliferation, migration and invasion, were examined using Cell Counting Kit-8, colony formation, wound healing and Transwell assays. The glycolysis level was determined based on the lactate release, glucose uptake, oxygen consumption rate and extracellular acidification rate. The binding relationship between ECT2 and ETS1 was verified using luciferase reporter and chromatin immunoprecipitation assays. The results indicated that ECT2 was highly expressed in prostate cancer cell lines. Knockdown of ECT2 expression could inhibit cell proliferation, migration, invasion and glycolysis. In addition, the transcription factor ETS1 could directly bind to the ECT2 promoter and positively regulate ECT2 expression. These data were combined with the results of rescue experiments and demonstrated that the inhibitory effects of the knockdown of ECT2 expression on the malignant behavior and glycolysis of prostate cancer cells were partially reversed by ETS1 overexpression. In conclusion, ETS1 induced transcriptional upregulation of ECT2 and enhanced the malignant biological behaviors of prostate cancer cells, thereby promoting the progression of prostate cancer. This evidence provides a theoretical basis for the treatment of prostate cancer.

Exercise Induced Immune Modulation - Consequences For Tumor Progression

Exercise Induced Immune Modulation - Consequences For Tumor Progression

Periprostatic adipose tissue inhibits tumor progression by secreting apoptotic factors: A natural barrier induced by the immune response during the early stages of prostate cancer.

Prostate cancer (PCa) is the second most prevalent malignancy in men worldwide. The risk factors for PCa include obesity, age and family history. Increased visceral fat has been associated with high PCa risk, which has prompted previous researchers to investigate the influence of body composition and fat distribution on PCa prognosis. However, there is a lack of studies focusing on the mechanisms and interactions between periprostatic adipose tissue (PPAT) and PCa cells. The present study investigated the association between the composition of pelvic adipose tissue and PCa aggressiveness to understand the role played by this tissue in PCa progression. Moreover, PPAT-conditioned medium (CM) was prepared to assess the influence of the PPAT secretome on the pathophysiology of PCa. The present study included 50 patients with localized PCa who received robot-assisted radical prostatectomy. Medical records were collected, magnetic resonance imaging scans were analyzed and body compositions were calculated to identify the associations between adipose tissue volume and clinical PCa aggressiveness. In addition, CM was prepared from PPAT and perivesical adipose tissue (PVAT) collected from 25 patients during surgery, and its effects on the PCa cell lines C4-2 and LNCaP, and the prostate epithelial cell line PZ-HPV-7, were investigated using a cell proliferation assay and RNA sequencing (RNA-seq). The results revealed that the initial prostate-specific antigen level was significantly correlated with pelvic and periprostatic adipose tissue volumes. In addition, PPAT volume was significantly higher in patients with extracapsular tumor extension. PCa cell proliferation was significantly reduced when the cells were cultured in PPAT-CM compared with when they were cultured in control- and PVAT-CM. RNA-seq revealed that immune responses, and the cell death and apoptosis pathways were enriched in PPAT-CM-cultured cells indicating that the cytokines or other factors secreted from PPAT-CM induced PCa cell apoptosis. These findings revealed that the PPAT secretome may inhibit PCa cell proliferation by activating immune responses and promoting cancer cell apoptosis. This mechanism may act as a first-line defense during the early stages of PCa.

SHR6390 Combined with Cabozantinib Inhibits Tumor Progression in the Hepatocellular Carcinoma Mouse Model.

A novel CDK4/6 inhibitor SHR6390 has shown significant anti-tumor effects. However, its role in hepatocellular carcinoma (HCC) remains unknown. To explore the inhibitory effect of combination treatment with SHR6390 and cabozantinib in HCC, and its antitumor mechanism, so as to provide a more effective therapeutic strategy for HCC patients. We investigated SHR6390, monotherapy or combined with cabozantinib, by CCK8, wound healing, transwell, western blotting, immunohistochemistry and mouse model of a subcutaneous tumor. Our results show that SHR6390 exhibited potent anti-proliferative activity against HCC in a dose-dependent manner. SHR6390 combined with cabozantinib exhibited more potent inhibition of cell viability, migration and invasion. In terms of potential mechanisms, we found that cabozantinib could lead to phosphorylation of Rb, which was reduced in SHR6390 and combined groups. SHR6390 monotherapy inhibited the growth of subcutaneous HCC tumors, besides, the combination treatment with SHR6390 and cabozantinib exerted synergistic anti-tumor activity in vivo Conclusion: SHR6390 is effective against HCC, monotherapy or combined with cabozantinib.

Preoperative systemic inflammatory response index as a prognostic marker for distal cholangiocarcinoma after pancreatoduodenectomy

BACKGROUND The relationship between preoperative inflammation status and tumorigenesis as well as tumor progression is widely acknowledged. AIM To assess the prognostic significance of preoperative inflammatory biomarkers in patients with distal cholangiocarcinoma (dCCA) who underwent pancreatoduodenectomy (PD). METHODS This single-center study included 216 patients with dCCA after PD between January 1, 2011, and December 31, 2022. The individuals were categorized into two sets based on their systemic inflammatory response index (SIRI) levels: A low SIRI group (SIRI < 1.5, n = 123) and a high SIRI group (SIRI ≥ 1.5, n = 93). Inflammatory biomarkers were evaluated for predictive accuracy using receiver operating characteristic curves. Both univariate and multivariate Cox proportional hazards analyses were performed to estimate SIRI for overall survival (OS) and recurrence-free survival (RFS). RESULTS The study included a total of 216 patients, with 58.3% being male and a mean age of 65.6 ± 9.6 years. 123 patients were in the low SIRI group and 93 were in the high SIRI group after PD for dCCA. SIRI had an area under the curve value of 0.674 for diagnosing dCCA, showing better performance than other inflammatory biomarkers. Multivariate analysis indicated that having a SIRI greater than 1.5 independently increased the risk of dCCA following PD, leading to lower OS [hazard ratios (HR) = 1.868, P = 0.006] and RFS (HR = 0.949, P < 0.001). Additionally, survival analysis indicated a significantly better prognosis for patients in the low SIRI group (P < 0.001). CONCLUSION It is determined that a high SIRI before surgery is a significant risk factor for dCCA after PD.

Personalized treatment of perihilar cholangiocarcinoma based on tumor genetic and molecular characteristics

This editorial discusses the article written by Tchilikidi et al that was published in the latest edition of the World Journal of Gastrointestinal Surgery . Genetic and molecular profiling of perihilar cholangiocarcinoma (pCCA) has identified a number of key abnormalities that drive tumor growth and spread, including pyruvate kinase M2, proline rich 11, and transcription factor 7, etc . pCCA has specific genetic and molecular features that can be used to develop personalized treatment plans. Personalized treatment approaches offer new opportunities for effectively targeting the underlying drivers of tumor growth and progression. The findings based on tumor genetic and molecular characteristics highlight the importance of developing personalized treatment strategies.

Abstract C111: Characterization of kisspeptin receptor signaling pathways in cervical cancer: Unveiling novel mechanisms and therapeutic potentials

Abstract Introduction: This study delves into the complex signaling mechanisms of the kisspeptin system in cervical cancer, aiming to unravel the intricate interactions between kisspeptin and its receptor, as well as their roles in modulating cancer progression. Given the emerging significance of the kisspeptin system in tumor biology, our research seeks to illuminate how kisspeptin signaling influences cellular behaviors critical to cancer development, such as proliferation and migration. By exploring the nuanced effects of kisspeptin receptor activation, this study contributes to a deeper understanding of its therapeutic potential and underscores the importance of kisspeptin pathways in the broader context of cancer research. Methods: Was employed Bioluminiscence Resonance Energy Transfer (BRET) assays to explore the activation of the kisspeptin receptor in cervical cancer cell lines, using synthesized analogs of kisspeptin-10 for detailed signaling analysis. Functional effects were assessed through proliferation and migration assays. Additionally, we evaluated the activation or reduction in phosphorylation of specific kinases involved in tumoral processes, providing a nuanced understanding of the signaling mechanisms at play. Results: Our data demonstrate that activation of the kisspeptin receptor substantially modulates cellular proliferation and motility in cervical cancer cell lines. We uncovered novel activation of the Gz protein by kisspeptin-10, which is integral to the kisspeptin receptor function, and identified an upregulation of signaling pathways critical for cell survival and metastasis. Importantly, we observed activation of kinases such as Chk2, c-Jun, p70 S6 kinase, and RSK 1/2/3, as well as members of the STAT family, following kisspeptin-10 stimulation. This kinase activation underscores the multifaceted role of kisspeptin in tumor progression, suggesting its involvement in both pro-oncogenic and tumor-suppressive pathways, and provides direct insights into the mechanistic underpinnings of kisspeptin effect on cancer cell behavior. Conclusion: In conclusion, our study elucidates the complex role of kisspeptin-10 in cervical cancer, demonstrating its ability to modulate cellular proliferation and motility through activation of the kisspeptin receptor. The novel activation of the Gz protein and subsequent upregulation of signaling pathways associated with cell survival and metastasis highlight the intricate involvement of kisspeptin in cancer progression. Furthermore, the activation of key kinases such as Chk2, c-Jun, p70 S6 kinase, RSK 1/2/3, and STAT family members upon kisspeptin-10 stimulation reveals a dual-faceted influence on tumor dynamics, promoting both pro-oncogenic and tumor-suppressive mechanisms. These findings provide significant insights into the molecular actions of kisspeptin in cervical cancer, offering potential targets for therapeutic intervention and a deeper understanding of its role in tumor biology. Citation Format: Deisy Y. Rodríguez-Sarmiento, Pedro H. Scarpelli-Pereira, Michel Bouvier. Characterization of kisspeptin receptor signaling pathways in cervical cancer: Unveiling novel mechanisms and therapeutic potentials [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C111.

Abstract C088: DARC/ACKR1 expression modulates immune regulation and influences tumor progression in triple-negative breast cancer

Abstract C088: DARC/ACKR1 expression modulates immune regulation and influences tumor progression in triple-negative breast cancer

ACSL6-activated IL-18R1-NF-κB promotes IL-18-mediated tumor immune evasion and tumor progression.

Aberrant activation of IL-18 signaling regulates tumor immune evasion and progression. However, the underlying mechanism remains unclear. Here, we report that long-chain acyl-CoA synthase 6 (ACSL6) is highly expressed in liver cancer and correlated with poor prognosis. ACSL6 promotes tumor growth, metastasis, and immune evasion mediated by IL-18, independent of its metabolic enzyme activity. Mechanistically, upon IL-18 stimulation, ACSL6 is phosphorylated by ERK2 at S674 and recruits IL-18RAP to interact with IL-18R1, thereby reinforcing the IL-18R1-IL-18RAP heterodimer and triggering NF-κB-dependent gene expression to facilitate tumor development. Furthermore, the up-regulation of CXCL1 and CXCL5 by ACSL6 promotes tumor-associated neutrophil and tumor-associated macrophage recruitment, thereby inhibiting cytotoxic CD8+ T cell infiltration. Ablation or S674A mutation of ACSL6 potentiated anti-PD-1 therapeutic efficacy by increasing the effector activity of intertumoral CD8+ T cells. We revealed that ACSL6 is a potential adaptor that activates IL-18-NF-κB axis-mediated tumor immune evasion and provides valuable insights for developing effective immunotherapy strategies for cancer.

Miniaturized protein profiling permits targeted signaling pathway analysis in individual circulating tumor cells to improve personalized treatment

BackgroundTraditional genomic profiling and mutation analysis of single cells like Circulating Tumor Cells (CTCs) fails to capture post-translational and functional alterations of proteins, often leading to limited treatment efficacy. To overcome this gap, we developed a miniaturized ‘protein analysis on the single cell level’ workflow—baptized ZeptoCTC. It integrates established technologies for single-cell isolation with sensitive Reverse Phase Protein Array (RPPA) analysis, thus enabling the comprehensive assessment of multiple protein expression and activation in individual CTCs.MethodsThe ZeptoCTC workflow involves several critical steps. Firstly, individual cells are labeled and isolated. This is followed by cell lysis and the printing of true single cell lysate preparations onto a ZeptoChip using a modified micromanipulator, CellCelector™. The printed lysates then undergo fluorescence immunoassay RPPA protein detection using a ZeptoReader. Finally, signal quantification is carried out with Image J software, ensuring precise measurement of multiple protein levels.ResultsThe efficacy of ZeptoCTC was demonstrated through various applications. Initially, it was used for measuring EpCAM protein expression, a standard marker for CTC detection, revealing higher levels in single MCF-7 over MDA-MB-231 tumor cells. Furthermore, in Capivasertib (Akt-inhibitor)-treated MCF-7 single cells, ZeptoCTC detected a 2-fold increase in the pAkt/Akt ratio compared to control cells, and confirmed co-performed bulk-cell western blot analysis results. Notably, when applied to individual CTCs from metastasized breast cancer patients, ZeptoCTC revealed significant differences in protein activation levels, particularly in measured pAkt and pErk levels, compared to patient-matched WBCs. Moreover, it successfully differentiated between CTCs from patients with different Akt1 genotypes, highlighting its potential to determine the activation status of druggable cancer driving proteins for individual and targeted treatment decision making.ConclusionsThe ZeptoCTC workflow represents a valuable tool in single cell cancer research, crucial for personalized medicine. It permits detailed analysis of key proteins and their activation status of targeted, cancer-driven signaling pathways in single cell samples, aiding in understanding tumor response, progression, and treatment efficacy beyond bulk analysis. The method significantly advances clinical investigations in cancer, improving treatment precision and effectiveness. The workflow will be applicable to protein analysis on other types of single cells like relevant in stem cell, neuropathology and hemopoietic cell research.

KDM4A promotes malignant progression of breast cancer by down-regulating BMP9 inducing consequent enhancement of glutamine metabolism

BackgroundRecent studies have found that histone-modified genes play an increasingly important role in tumor progression. Lysine(K) specific demethylase 4A (KDM4A) is a histone lysine-specific demethylase highly expressed in a variety of malignant tumors, data showed that KDM4A was negatively correlated with the Bone Morphogenetic Protein 9 (BMP9) in breast cancer. And previous experiments have demonstrated that exogenous BMP9 significantly inhibits breast cancer development.Materials and methodsWe detected the expression of KDM4A in breast cancer and the relationship between KDM4A and BMP9 using real-time quantitative PCR (RT-qPCR) and Western blot, and verified the interaction between KDM4A and BMP9 by ChIP experiments. At the same time, we also detected whether KDM4A had effects on the RNA and protein stability of BMP9 using actinomycin D and cycloheximide. Measurement of alpha-ketoglutarate (α-KG) level by ELISA to observe the effect of BMP9 on glutamine metabolism in breast cancer cells. Nucleoplasmic distribution of KDM4A after exogenous BMP9 treatment in breast cancer cells were observed by immunofluorescence staining and Western blot. A subcutaneous xenograft tumor model in nude mice was used to study the therapeutic effects of exogenous BMP9 and KDM4A inhibitor (JIB-04) in breast cancer. CCK-8, conoly formation, Transwell, wound healing, and immunohistochemistry were used to monitor the growth of tumor and cell function.ResultsWe found that KDM4A was abnormally highly expressed in breast cancer, and silenced BMP9 expression by removing histone methyl groups from the BMP9 gene region. Meanwhile, KDM4A could also reduce the stability of BMP9 protein. BMP9 inhibit glutamine metabolism in breast cancer, resulting in a decrease in its product α-KG, is confirmed by ELISA. Altered nucleoplasmic distribution of KDM4A due to decreased α-KG was confirmed by immunofluorescence staining and Western blot. Animal experiments confirm that the combination of exogenous BMP9 and JIB-04 shows significantly better results in breast cancer.ConclusionsKDM4A silences BMP9 expression by removing histone methyl groups from the BMP9 gene region, leading to further enhancement of glutamine metabolism, which contributes to malignant tumor progression. In addition, using JIB-04 in combination with exogenous BMP9 could inhibit the malignant progression of breast cancer cells and the growth of tumors more significantly.

Kindlin-2 regulates the oncogenic activities of integrins and TGF-β in triple-negative breast cancer progression and metastasis

AbstractKindlin-2, an adapter protein, is dysregulated in various human cancers, including triple-negative breast cancer (TNBC), where it drives tumor progression and metastasis by influencing several cancer hallmarks. One well-established role of Kindlin-2 involves the regulation of integrin signaling, achieved by directly binding to the cytoplasmic tail of the integrin β subunit. In this study, we present novel insights into Kindlin-2’s involvement in stabilizing the β1-Integrin:TGF-β type 1 receptor (TβRI) complexes, acting as a physical bridge that links β1-Integrin to TβRI. Loss of Kindlin-2 results in the degradation of this protein complex, leading to the inhibition of downstream oncogenic pathways. We used a diverse range of in vitro assays, including CRISPR/Cas9 gene editing, cell migration, 3D-tumorsphere formation and invasion, solid binding, co-immunoprecipitation, cell adhesion and spreading assays, as well as western blot and flow cytometry analyses, utilizing MDA-MB-231 and 4T1 TNBC cell lines. Additionally, preclinical in vivo mouse models of TNBC tumor progression and metastasis were employed to substantiate our findings. Our studies established the direct interaction between Kindlin-2 and β1-Integrin and between Kindlin-2 and TβRI. Disruption of these interactions, via CRISPR/Cas9-mediated knockout of Kindlin-2, led to the degradation of β1-Integrin and TβRI, resulting in the inhibition of oncogenic pathways downstream of both proteins, subsequently hindering tumor growth and metastasis. Treatment of Kindlin-2-deficient cells with the proteasome inhibitor MG-132 restored the expression of both β1-Integrin and TβRI. Furthermore, the rescue of Kindlin-2 expression reinstated their oncogenic activities in vitro and in vivo, while Kindlin-2 lacking domains involved in the interaction of Kindlin-2 with β1-Integrin or TβRI did not. This study identifies a novel function of Kindlin-2 in stabilizing the β1-Integrin:TβRI complexes and regulating their downstream oncogenic signaling. The translational implications of these findings are substantial, potentially unveiling new therapeutically targeted pathways crucial for the treatment of TNBC tumors.

A New Perspective on Tumor Progression: Evolution via Selection for Function

Abstract Tumorigenesis is commonly attributed to Darwinian processes involving natural selection among cells and groups of cells. However, progressing tumors are those that also achieve an appropriate group phenotypic composition (GPC). Yet, the selective processes acting on tumor GPCs are distinct from that associated with classical Darwinian evolution (i.e., natural selection based on differential reproductive success) as tumors are not genuine evolutionary individuals and do not exhibit heritable variation in fitness. This complex evolutionary scenario is analogous to the recently proposed concept of “selection for function” invoked for the evolution of both living and non-living systems. Therefore, we argue that it is inaccurate to assert that Darwinian processes alone account for all the aspects characterizing tumorigenesis and cancer progression; rather, by producing the genetic and phenotypic diversity required for creating novel GPCs, these processes fuel the evolutionary success of tumors that is dependent on selection for function at the tumor level.

In vivo CRISPR screens identify Mga as an immunotherapy target in triple-negative breast cancer

Immune evasion is not only critical for tumor initiation and progression, but also determines the efficacy of immunotherapies. Through iterative in vivo CRISPR screens with seven syngeneic tumor models, we identified core and context-dependent immune evasion pathways across cancer types. This valuable high-confidence dataset is available for the further understanding of tumor intrinsic immunomodulators, which may lead to the discovery of effective anticancer therapeutic targets. With a focus on triple-negative breast cancer (TNBC), we found that Mga knock-out significantly enhances antitumor immunity and inhibits tumor growth. Transcriptomics and single-cell RNA sequencing analyses revealed that Mga influences various immune-related pathways in the tumor microenvironment. Our findings suggest that Mga may play a role in modulating the tumor immune landscape, though the precise mechanisms require further investigation. Interestingly, we observed that low MGA expression in breast cancer patients correlates with a favorable prognosis, particularly in those with active interferon-γ signaling. These observations provide insights into tumor immune escape mechanisms and suggest that further exploration of MGA’s function could potentially lead to effective therapeutic strategies in TNBC.

Tumour stemness and poor clinical outcomes in haemochromatosis patients with hepatocellular carcinoma

AimsPatients with haemochromatosis (HFE) are known to have an increased risk of developing hepatocellular carcinoma (HCC). Available data are conflicting on whether such patients have poorer prognosis, and there is...

Complex role of neutrophils in the tumor microenvironment: an avenue for novel immunotherapies

Neutrophils, which originate from the bone marrow and are characterized by a segmented nucleus and a brief lifespan, have a crucial role in the body’s defense against infections and acute inflammation. Recent research has uncovered the complex roles of neutrophils as regulators in tumorigenesis, during which neutrophils exhibit a dualistic nature that promotes or inhibits tumor progression. This adaptability is pivotal within the tumor microenvironment (TME). In this review, we provide a comprehensive characterization of neutrophil plasticity and heterogeneity, aiming to illuminate current research findings and discuss potential therapeutic avenues. By delineating the intricate interplay of neutrophils in the TME, this review further underscores the urgent need to understand the dual functions of neutrophils with particular emphasis on the anti-tumor effects to facilitate the development of effective therapeutic strategies against cancer.

Inhalation Anesthetics Play a Janus-Faced Role in Self-Renewal and Differentiation of Stem Cells

Inhalation anesthesia stands as a pivotal modality within clinical anesthesia practices. Beyond its primary anesthetic effects, inhaled anesthetics have non-anesthetic effects, exerting bidirectional influences on the physiological state of the body and disease progression. These effects encompass impaired cognitive function, inhibition of embryonic development, influence on tumor progression, and so forth. For many years, inhaled anesthetics were viewed as inhibitors of stem cell fate regulation. However, there is now a growing appreciation that inhaled anesthetics promote stem cell biological functions and thus are now regarded as a double-edged sword affecting stem cell fate. In this review, the effects of inhaled anesthetics on self-renewal and differentiation of neural stem cells (NSCs), embryonic stem cells (ESCs), and cancer stem cells (CSCs) were summarized. The mechanisms of inhaled anesthetics involving cell cycle, metabolism, stemness, and niche of stem cells were also discussed. A comprehensive understanding of these effects will enhance our comprehension of how inhaled anesthetics impact the human body, thus promising breakthroughs in the development of novel strategies for innovative stem cell therapy approaches.

GRB7-mediated enhancement of cell malignant characteristics induced by Helicobacter pylori infection

Growth factor receptor bound protein 7 (GRB7) is reportedly upregulated in human gastric cancer (GC), which is closely associated with tumor progression and prognosis. However, the mechanism underlying its dysregulation in GC remains poorly understood. In this study, we found that GRB7 overexpression was associated with Helicobacter pylori (H. pylori) infection. GC cells (AGS and MGC-803) infection assays revealed that this upregulation was mediated by the transcription factor STAT3, and activation of STAT3 by H. pylori promoted GRB7 expression in infected GC cells. Moreover, CagA, the key virulence factor of H. pylori, was found involved in STAT3-mediated GRB7 overexpression. The overexpressed GRB7 further promoted GC cell proliferation, migration, and invasion by activating ERK signaling. Mice infection was further used to investigate the action of GRB7. In H. pylori infection, GRB7 expression in mice gastric mucosa was elevated, and higher STAT3 and ERK activation were also detected. These results revealed GRB7-mediated pathogenesis in H. pylori infection, in which H. pylori activates STAT3, leading to increased GRB7 expression, then promotes activation of the ERK signal, and finally enhances malignant properties of infected cells. Our findings elucidate the role of GRB7 in H. pylori-induced gastric disorders, offering new prospects for the treatment and prevention of H. pylori-associated gastric carcinogenesis by targeting GRB7.