Role of Epithelial to Mesenchymal Transition in Colorectal Cancer

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14815 - 14815

Published: Oct. 1, 2023

The epithelial–mesenchymal transition (EMT) is a cellular reprogramming process that occurs during embryonic development and adult tissue homeostasis. This involves epithelial cells acquiring mesenchymal phenotype. Through EMT, cancer acquire properties associated with more aggressive EMT its opposite, mesenchymal–epithelial (MET), have been described in tumors over the past ten years, including colorectal (CRC). When activated, expression of marker E-cadherin decreased vimentin raised. As result, temporarily take on phenotype, becoming motile promoting spread tumor cells. Epithelial–mesenchymal plasticity (EMP) has become hot issue CRC because strong inducers (such as transforming growth factor β, TGF-β) can initiate regulate metastasis, microenvironment, immune system resistance CRC. In this review, we into account significance EMT-MET impact cells’ prognosis analysis connection between stem (CCSCs) will help to further clarify current meager understandings EMT. Recent advances affecting important transcription factors CCSCs are highlighted. We come conclusion regulatory network for complicated, great deal crosstalk alternate paths. More thorough research required effectively connect clinical management biomarkers targeted treatments

Language: Английский

---

Single-cell sequencing of ascites fluid illustrates heterogeneity and therapy-induced evolution during gastric cancer peritoneal metastasis

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 14, 2023

Abstract Peritoneal metastasis is the leading cause of death for gastrointestinal cancers. The native and therapy-induced ascites ecosystems are not fully understood. Here, we characterize single-cell transcriptomes 191,987 cancer/immune cells from 35 patients with/without gastric cancer peritoneal (GCPM). During GCPM progression, an increase seen monocyte-like dendritic (DCs) that pro-angiogenic with reduced antigen-presenting capacity correlate poor (GC) prognosis. We also describe evolution DCs regulatory proliferative T following therapy. Moreover, track GC evolution, identifying high-plasticity clusters exhibit a propensity to shift high-proliferative phenotype. Transitions occur via recently described, autophagy-dependent plasticity program, paligenosis. Two autophagy-related genes ( MARCKS TXNIP ) mark poorer prognosis, autophagy inhibitors induce apoptosis in patient-derived organoids. Our findings provide insights into developmental trajectories underlying progression therapy resistance.

Language: Английский

---

GPCR drug discovery: new agents, targets and indications

Nature Reviews Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Language: Английский

---

The Cytokine Network in Colorectal Cancer: Implications for New Treatment Strategies

Cells, Journal Year: 2022, Volume and Issue: 12(1), P. 138 - 138

Published: Dec. 29, 2022

Colorectal cancer (CRC) is one of the most frequent tumor entities worldwide with only limited therapeutic options. CRC not a genetic disease several mutations in specific oncogenes and/or suppressor genes such as APC, KRAS, PIC3CA, BRAF, SMAD4 or TP53 but also multifactorial including environmental factors. Cancer cells communicate their environment mostly via soluble factors cytokines, chemokines growth to generate favorable microenvironment (TME). The TME, heterogeneous population differentiated and progenitor cells, plays critical role regulating development, growth, invasion, metastasis therapy resistance. In this context, cytokines from TME influence each other, eliciting an inflammatory milieu that can either enhance suppress metastasis. Additionally, lines evidence exist composition microbiota regulates processes, controlled by cytokine secretion, play carcinogenesis progression. review, we discuss networks between microbiome colorectal related treatment strategies, goal cytokine-mediated strategies could overcome common resistance tumors.

Language: Английский

---

T Cells in Colorectal Cancer: Unravelling the Function of Different T Cell Subsets in the Tumor Microenvironment

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11673 - 11673

Published: July 19, 2023

Therapeutic options for metastatic colorectal cancer (mCRC) are very limited, and the prognosis using combination therapy with a chemotherapeutic drug targeted agent, e.g., epidermal growth factor receptor or tyrosine kinase, remains poor. Therefore, mCRC is associated poor median overall survival (mOS) of only 25–30 months. Current immunotherapies checkpoint inhibitor blockade (ICB) have led to substantial change in treatment several cancers, such as melanoma non-small cell lung cancer. In CRC, ICB has limited effects, except patients microsatellite instability-high (MSI-H) mismatch repair-deficient (dMMR) tumors, which comprise about 15% sporadic CRC 4% CRC. The vast majority CRCs microsatellite-stable (MSS) tumors low levels infiltrating immune cells, immunotherapy no clinical benefit so far. Immunotherapy inhibitors requires presence T cells into tumor microenvironment (TME). This makes most important effector TME, evidenced by establishment immunoscore—a method estimate patients. contains types that anti-tumorigenic, CD8+ pro-tumorigenic, regulatory (Tregs) helper 17 (Th17) cells. However, even show marked heterogeneity, they can become exhausted, enter state hyporesponsiveness dysfunctional express high molecules, targets ICB. To kill need recognition MHC class I, often downregulated on this case, population unconventional γδ overcome limitations conventional an αβT receptor. recognize antigens MHC-independent manner, thus acting bridge between innate adaptive immunity. Here, we discuss effects different subsets special emphasis possibility them CAR-T therapy. We explain exclusion possibilities enable these “cold” tumors.

Language: Английский

---

Levels of systemic inflammation response index are correlated with tumor-associated bacteria in colorectal cancer

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 30, 2023

The relationship between systemic inflammation and tumor-associated bacteria is largely unknown in colorectal cancer (CRC). primary aim of this study was to investigate the prognostic effects response index (SIRI) on survival outcomes CRC patients who experienced surgical therapy, second reveal potential association SIRI levels CRC. We recruited a cohort 298 resection Wuhan Union Hospital. These were assigned low high groups based cut-off value SIRI. utilized 1:1 propensity score matching (PSM) reduce confounding factors group (N = 83) 83). total DNA 166 paraffin-embedded tumor tissues 24 frozen extracted amplified, 16 S rRNA sequencing employed uncover composition microbiota groups. Survival analysis uncovered that exhibited significantly shorter overall disease-free time than companions after PSM. ROC analyses showed prediction abilities much higher other serum inflammatory biomarkers for outcomes. microbial richness diversity remarkably those group. At phylum level, we found Proteobacteria, Synergistetes, WPS-2, Thermil, Fusobacteria enriched Cupriavidus, Thermus, Ochrobactrum, Acidovorax at genus level. samples also obtained similar results. promising novel biomarker among sufferers underwent removal. There existed significant differences compositions

Language: Английский

---

The role of macrophages in the tumor microenvironment and tumor metabolism

Seminars in Immunopathology, Journal Year: 2023, Volume and Issue: 45(2), P. 187 - 201

Published: March 1, 2023

Language: Английский

---

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

---

Polymeric nanoparticles in colorectal cancer

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 203 - 231

Published: Jan. 1, 2024

Language: Английский

---

Molecular understanding and clinical aspects of tumor-associated macrophages in the immunotherapy of renal cell carcinoma

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: Aug. 22, 2024

Abstract Renal cell carcinoma (RCC) is one of the most common tumors that afflicts urinary system, accounting for 90–95% kidney cancer cases. Although its incidence has increased over past decades, pathogenesis still unclear. Tumor-associated macrophages (TAMs) are prominent immune cells in tumor microenvironment (TME), comprising more than 50% volume. By interacting with cells, TAMs can be polarized into two distinct phenotypes, M1-type and M2-type TAMs. In TME, TAMs, which known to promote tumorigenesis, abundant suppress growth. This ratio M1 M2 create an immunosuppressive environment contributes progression survival. review focused on role RCC, including their polarization, impacts proliferation, angiogenesis, invasion, migration, drug resistance, immunosuppression. addition, we discussed potential targeting clinical therapy RCC. A deeper understanding molecular biology essential exploring innovative therapeutic strategies treatment

Language: Английский

---