Insights into the Tumor Microenvironment—Components, Functions and Therapeutics

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(24), P. 17536 - 17536

Published: Dec. 15, 2023

Similarly to our healthy organs, the tumor tissue also constitutes an ecosystem. This implies that stromal cells acquire altered phenotype in tandem with cells, thereby promoting survival. Cancer are fueled by abnormal blood vessels, allowing them develop and proliferate. Tumor-associated fibroblasts adapt their cytokine chemokine production needs of alter peritumoral stroma generating more collagen, stiffening matrix; these processes promote epithelial-mesenchymal transition cell invasion. Chronic inflammation mobilization pro-tumorigenic inflammatory further facilitate expansion. All events can impede effective administration treatment; so, successful inhibition tumorous matrix remodeling could enhance success antitumor therapy. Over last decade, significant progress has been made introduction novel immunotherapy targets inhibitory mechanisms T activation. However, extensive research is being conducted on components other types microenvironment (TME) may serve as potential therapeutic targets.

Language: Английский

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Ubiquitin-specific proteases: From biological functions to potential therapeutic applications in gastric cancer

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116323 - 116323

Published: Feb. 23, 2024

Deubiquitination, a post-translational modification regulated by deubiquitinases, is essential for cancer initiation and progression. Ubiquitin-specific proteases (USPs) are elements of the deubiquitinase family, overexpressed in gastric (GC). Through regulation several signaling pathways, such as Wnt/β-Catenin nuclear factor-κB signaling, promotion expression deubiquitination- stabilization-associated proteins, USPs promote proliferation, metastasis, invasion, epithelial-mesenchymal transition GC. In addition, closely related to clinicopathological features, patient prognosis, chemotherapy resistance. therefore could be used prognostic biomarkers. USP targeting small molecule inhibitors have demonstrated strong anticancer activity. However, they not yet been tested clinic. This article provides an overview latest fundamental research on GC, aiming enhance understanding how contribute GC progression, identifying possible targets treatment improve survival.

Language: Английский

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Pancreatic cancer cells infiltrate nerves through TGFbeta1-driven perineural epithelial-to-mesenchymal-like transdifferentiation

Neoplasia, Journal Year: 2025, Volume and Issue: 60, P. 101126 - 101126

Published: Jan. 21, 2025

Language: Английский

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Signaling pathways in colorectal cancer implications for the target therapies

Molecular Biomedicine, Journal Year: 2024, Volume and Issue: 5(1)

Published: June 7, 2024

Abstract Colorectal carcinoma (CRC) stands as a pressing global health issue, marked by the unbridled proliferation of immature cells influenced multifaceted internal and external factors. Numerous studies have explored intricate mechanisms tumorigenesis in CRC, with primary emphasis on signaling pathways, particularly those associated growth factors chemokines. However, sheer diversity molecular targets introduces complexity into selection targeted therapies, posing significant challenge achieving treatment precision. The quest for an effective CRC is further complicated absence pathological insights mutations or alterations occurring tumor cells. This study reveals transfer from cell membrane to nucleus, unveiling recent advancements this crucial cellular process. By shedding light novel dimension, research enhances our understanding intricacies underlying providing potential avenue breakthroughs therapeutic strategies. In addition, comprehensively outlines immune responses incited aberrant activation specific focus cells, cytokines, their collective impact dynamic landscape drug development. not only contributes significantly advancing medicine but also lays groundwork future clinical trials, fostering optimism improved outcomes refined approaches combating colorectal carcinoma.

Language: Английский

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Roles of Post-Translational Modifications of Transcription Factors Involved in Breast Cancer Hypoxia

Molecules, Journal Year: 2025, Volume and Issue: 30(3), P. 645 - 645

Published: Feb. 1, 2025

BC is the most commonly diagnosed cancer and second leading cause of death among women worldwide. Cellular stress a condition that leads to disrupted homeostasis by extrinsic intrinsic factors. Among other stressors, hypoxia driving force for breast (BC) progression general hallmark solid tumors. Thus, intratumoral an important determinant invasion, metastasis, treatment failure, prognosis, patient mortality. Acquisition epithelial–mesenchymal transition (EMT) phenotype also consequence tumor hypoxia. The cellular response mainly regulated signaling pathway, governed hypoxia-inducible factors (HIFs), HIF1α. HIFs are family transcription (TFs), which induce expression target genes involved in cell survival proliferation, metabolic reprogramming, angiogenesis, resisting apoptosis, metastasis. HIF1α cooperates with large number TFs. In this review, we focused on crosstalk cooperation between TFs BC. We identified cluster TFs, proposed as HIF1α-TF interactome, orchestrates hypoxia, due their post-translational modifications (PTMs), including phosphorylation/dephosphorylation, ubiquitination/deubiquitination, SUMOylation, hydroxylation, acetylation, S-nitrosylation, palmitoylation. PTMs these HIF1α-related drive stability activity, degradation turnover, bidirectional translocation cytoplasm or plasma membrane nucleus cells, well transcription/activation proteins encoded oncogenes inactivation suppressor genes. Consequently, interactome crucial regulatory mechanisms oxygen deprivation cells.

Language: Английский

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Exploring TGF-β Signaling in Cancer Progression: Prospects and Therapeutic Strategies

OncoTargets and Therapy, Journal Year: 2025, Volume and Issue: Volume 18, P. 233 - 262

Published: Feb. 1, 2025

Cancer persists as a ubiquitous global challenge despite the remarkable advances. It is caused by uncontrolled cell growth and metastasis. The Transforming Growth Factor-beta (TGF-β) signaling pathway considered primary regulator of various normal physiological processes in human body. Recently, factors determining nature TGF-β response have received attention, specifically its which can be an attractive therapeutic target for cancer treatments. receptor activated ligands undergoes transduction signals via canonical (SMAD dependent) or non-canonical independent) pathways regulating several cellular functions. Furthermore, cross talk with other has shown controlled regulation This review highlights between major TGF-β. These include Wnt, NF-κB, PI3K/Akt, Hedgehog (Hh). dual role at different stages. suppress tumor formation early stages promote progression advanced complex behaviour made it promising interventions. Moreover, many strategies been designed to control levels, inhibiting tumor-promoting while enhancing tumor-suppressive effects, each unique molecular mechanisms clinical implications. also discusses inhibitors including ligand traps, small molecule (SMIs), monoclonal antibodies (mAbs), antisense oligonucleotides specific components inhibit are studied both preclinical trials types cancer. prospect physiology case dysregulation, inhibitors, effects therapy along perspective combinational therapies treat

Language: Английский

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Association between SMAD3 and SMAD7 gene polymorphisms and susceptibility to stress urinary incontinence in Chinese women

American Journal of Translational Research, Journal Year: 2025, Volume and Issue: 17(2), P. 1097 - 1105

Published: Jan. 1, 2025

This study aimed to investigate the correlation between single nucleotide polymorphisms (SNPs) in SMAD3 and SMAD7 genes genetic risk of stress urinary incontinence (SUI) Chinese women. A case-control was conducted with 117 women diagnosed SUI 103 healthy controls. SNPs (rs28683050, rs12901499) (rs12953717, rs4939827) were analyzed using polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP). Allele genotype frequencies assessed SHEsis online platform. Epidemiological, clinical, laboratory data collected retrospectively. patients underwent pelvic floor muscle training (PFMT), treatment outcomes evaluated after 3 months. The G allele GG rs12901499 significantly more common case group (p_allele < 0.001, p_genotype = 0.002). Similarly, T TT at rs12953717 frequent 0.002, 0.007). Multivariate logistic regression revealed that body mass index (BMI), family history, significant factors for (P 0.05). Furthermore, associated poorer PFMT outcomes. Our findings suggest are potential Additionally, may influence effectiveness treatment.

Language: Английский

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Downregulation of SMAD2 and SMAD4 is associated with poor prognosis and shorter survival in esophageal squamous cell carcinoma

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: March 3, 2025

Language: Английский

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Fruquintinib inhibits the migration and invasion of colorectal cancer cells by modulating epithelial-mesenchymal transition via TGF-β/Smad signaling pathway

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: March 11, 2025

Background Fruquintinib, a selective vascular endothelial growth factor receptor (VEGFR) inhibitor, has shown considerable efficacy in colorectal cancer (CRC) treatment. Despite its promising therapeutic effects, the precise molecular mechanisms underlying effects remain incompletely understood. In this study, we explored functional roles and of fruquintinib CRC therapy. Material methods Human cells (HCT-116 LOVO) were cultured treated with fruquintinib. Cell counting kit-8 assay kit (CCK-8) colony formation assays performed to investigate on cell proliferation. Wound healing transwell conducted explore role migration invasion. RNA sequencing bioinformatics analysis was used potential mechanism development CRC. Western blot measure protein level. Results Fruquintinib significantly inhibited proliferation, migration, invasion cells. Bioinformatics indicated that modulated epithelial-mesenchymal transition (EMT) pathway, experimental validation confirmed regulatory core EMT-associated biomarkers. Notably, treatment resulted upregulation E-cadherin downregulation N-cadherin, vimentin, MMP9. revealed dose-dependently suppressed SMAD2/3 expression. TGF-β agonist KRFK TFA attenuated fruquintinib’s effect, reversing as well downregulatin N-cadherin SMAD2/3. Additionally, partially restored assays, counteracting inhibitory impact. Conclusion These findings indicate effectively hampers by disrupting EMT process via TGF-β/Smad signaling pathway. This study sheds light which inhibits progression underscores for further clinical investigation.

Language: Английский

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In-silico analysis unveiling the role of cancer stem cells in immunotherapy resistance of immune checkpoint-high pancreatic adenocarcinoma

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 26, 2025

Although immune checkpoint (IC) inhibition is a major treatment modality in cancer-immunotherapy, multiple cancers show low response. Our in-silico exploration by mining cancer datasets using R2, available clinical trial data, and Kaplan–Meier analysis from GEPIA depicted that unlike low-responder (LR) cancers, high-responder (HR) furnish higher IC expression, upon lowering may provide better prognosis. Contrastingly, pancreatic adenocarcinoma (PAAD) demonstrated high expression but immunotherapy-response. Infiltration scores TIMER2.0 revealed pro-tumor subsets cancer-associated fibroblasts (CAFs) while depicting lower anti-tumor PAAD as compared to HR lung (LUAD). Additionally, bioinformatic tool cBioportal showed lesser tumor mutational burden, mismatch repair deficiency greater percent of driver mutations TP53, KRAS CDKN2A PAAD, supporting its immunotherapy-resistance than LUAD. search for the 'key' immunotherapy response-deciding factor(s) stem cells (CSCs), known contributors therapy-resistance immuno-evasion, be positively correlated with above-mentioned mutations, CAF subsets; furnished CSC genes UMAP/tSNE analyses signature pro-cancer cells, negatively cytotoxic-T PAAD. study explains immunotherapy-response IC-expressing wherein plays pivotal role. Further portrayed correlation CSCs other LR too, substantiating need personalized evaluation targeting successful outcomes.

Language: Английский

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