Periodontitis and progression of gastrointestinal cancer: current knowledge and future perspective DOI
Kamyar Nasiri,

Masoud Amiri Moghaddam,

Enas Abdalla Etajuri

et al.

Clinical & Translational Oncology, Journal Year: 2023, Volume and Issue: 25(10), P. 2801 - 2811

Published: April 10, 2023

Language: Английский

Potential effects of gut microbiota on host cancers: focus on immunity, DNA damage, cellular pathways, and anticancer therapy DOI Creative Commons
Jiaao Sun, Feng Chen, Guangzhen Wu

et al.

The ISME Journal, Journal Year: 2023, Volume and Issue: 17(10), P. 1535 - 1551

Published: Aug. 8, 2023

Abstract The symbiotic bacteria that live in the human gut and metabolites they produce have long influenced local systemic physiological pathological processes of host. microbiota are increasingly being recognized for its impact on a range diseases, including cancer, it may play key role occurrence, progression, treatment, prognosis many types cancer. Understanding functional cancer is crucial development era personalized medicine. Here, we review recent advances research summarize important associations clear experimental evidence variety cancers, focus application possible challenges associated with antitumor therapy. In conclusion, our demonstrated multifaceted mechanisms affecting provides directions ideas future clinical research.

Language: Английский

Citations

47

Fusobacterium nucleatum promotes colorectal cancer liver metastasis via miR-5692a/IL-8 axis by inducing epithelial-mesenchymal transition DOI Creative Commons
Yulong Yu,

Han Yin,

Bili Wu

et al.

Journal of Biomedical Science, Journal Year: 2025, Volume and Issue: 32(1)

Published: Jan. 6, 2025

Abstract Background The association between the intestinal microbiota and colorectal cancer (CRC) has been extensively studied, with Fusobacterium nucleatum ( F. , FN) being found in high abundance tissues. Previous research emphasized significant role of occurrence CRC. However, impact on CRC liver metastasis not well understood. Methods effects ability cell were evaluated vitro examined by wound-healing assay transwell assay. mouse model was constructed spleen injection, degree assessed vivo bioluminescence imaging. gene expression changes cells after co-culture analyzed through transcriptome sequencing. qRT-PCR Western Blot assays performed to validate related genes proteins. Results significantly enhanced vitro. In model, also promoted development Mechanistically, infection increased IL-8 downregulated level miR-5692a, a regulatory microRNA IL-8. This led activation ERK pathway resulted epithelial-mesenchymal transition (EMT) cells. Conclusions Our results suggest that promotes inducing miR-5692a/IL-8 axis. These findings provide new insights for prevention treatment metastasis.

Language: Английский

Citations

4

Gut Microbiota Secondary Metabolites: Key Roles in GI Tract Cancers and Infectious Diseases DOI Creative Commons

Eman K. E. Anwer,

Muhammad Ajagbe,

Mohamed Sherif

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 100 - 100

Published: Jan. 3, 2025

The gut microbiota, a dynamic ecosystem of trillions microorganisms, produces secondary metabolites that profoundly influence host health. Recent research has highlighted the significant role these metabolites, particularly short-chain fatty acids, indoles, and bile in modulating immune responses, impacting epigenetic mechanisms, contributing to disease processes. In gastrointestinal (GI) cancers such as colorectal, liver, gastric cancer, microbial can drive tumorigenesis by promoting inflammation, DNA damage, evasion. Conversely, same hold therapeutic promise, potentially enhancing responses chemotherapy immunotherapy even directly suppressing tumor growth. addition, play crucial roles infectious susceptibility resilience, mediating pathways impact pathogen resistance. By consolidating recent insights into microbiota's shaping health, this review underscores potential targeting microbiome-derived for treating GI diseases calls further microbiome-based interventions.

Language: Английский

Citations

3

Intracellular Fusobacterium nucleatum infection attenuates antitumor immunity in esophageal squamous cell carcinoma DOI Creative Commons
Yiqiu Li,

Shan Xing,

Fangfang Chen

et al.

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

Published: Sept. 18, 2023

Currently, the influence of tumor microbiome on effectiveness immunotherapy remains largely unknown. Intratumoural Fusobacterium nucleatum (Fn) functions as an oncogenic bacterium and can promote progression in esophageal squamous cell carcinoma (ESCC). Our previous study revealed that Fn is a facultative intracellular its virulence factor Fn-Dps facilitates survival Fn. In this study, we find DNA enriched nonresponder (NR) group among ESCC patients receiving PD-1 inhibitor serum antibody level significantly higher NR than responder (R) group. addition, infection has opposite impact efficacy αPD-L1 treatment animals. Mechanistically, confirm inhibit proliferation cytokine secretion T cells binds to PD-L1 gene promoter activating transcription factor-3 (ATF3) transcriptionally upregulate expression. results suggest it may be important therapeutic strategy eradicate intratumoral before initiating immunotherapies.

Language: Английский

Citations

37

Cell membrane-camouflaged bufalin targets NOD2 and overcomes multidrug resistance in pancreatic cancer DOI Creative Commons
Wei Zhang,

Yibao Fan,

Jinze Zhang

et al.

Drug Resistance Updates, Journal Year: 2023, Volume and Issue: 71, P. 101005 - 101005

Published: Aug. 21, 2023

Multidrug resistance in pancreatic cancer poses a significant challenge clinical treatment. Bufalin (BA), compound found secretions from the glands of toads, may help overcome this problem. However, severe cardiotoxicity thus far has hindered its application. Hence, present study aimed to develop cell membrane-camouflaged and BA-loaded polylactic-co-glycolic acid nanoparticle (CBAP) assess potential counter chemoresistance cancer.The toxicity CBAP was evaluated by electrocardiogram, body weight, distress score, nesting behavior mice. In addition, anticarcinoma activity underlying mechanism were investigated both vitro vivo.CBAP significantly mitigated BA-mediated acute enhanced sensitivity several drugs, such as gemcitabine, 5-fluorouracil, FOLFIRINOX. Mechanistically, directly bound nucleotide-binding oligomerization domain containing protein 2 (NOD2) inhibited expression nuclear factor kappa-light-chain-enhancer activated B cells. This inhibits ATP-binding cassette transporters, which are responsible for cells.Our findings indicate that NOD2. Combining with standard-of-care chemotherapeutics represents safe efficient strategy treatment cancer.

Language: Английский

Citations

33

Fusobacterium nucleatum promotes esophageal squamous cell carcinoma progression and chemoresistance by enhancing the secretion of chemotherapy-induced senescence-associated secretory phenotype via activation of DNA damage response pathway DOI Creative Commons
Jianwei Zhang, Dan Zhang, Haisen Yin

et al.

Gut Microbes, Journal Year: 2023, Volume and Issue: 15(1)

Published: April 5, 2023

Senescence frequently occurs in cancer cells response to chemotherapy (called therapy-induced senescence). Senescent can exert paracrine effects through the senescence-associated secretory phenotype (SASP) promoting recurrence and chemoresistance. The altered gut microbiota has been closely associated with progression direct interaction cells. However, little is known about relationship between senescent This study aimed explore impact of on SASP. We found that esophageal squamous cell carcinoma (ESCC) were induced into senescence following platinum-based chemotherapy, accompanied by secretion a robust Furthermore, ESCC exerted tumor-promoting effect SASP both vitro vivo. Through 16S rRNA gene sequencing fluorescence situ hybridization, we identified Fusobacterium nucleatum (F. nucleatum) was abundant human cancerous tissues correlated poor prognosis patients. Notably, F. further promoted Compared conditioned medium from cells, nucleatum-treated accelerated tumor growth xenograft models, enhanced migration invasion abilities, potentiated chemoresistance Mechanistically, invaded survived an increase DNA damage activate pathway, thus enhancing Altogether, these findings reveal for first time promotes chemotherapy-induced drive chemoresistance, which supports as potential target therapy.

Language: Английский

Citations

31

NOD-like Receptor Signaling Pathway in Gastrointestinal Inflammatory Diseases and Cancers DOI Open Access
Yujie Zhou,

Songyan Yu,

Wenyong Zhang

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14511 - 14511

Published: Sept. 25, 2023

Nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) are intracellular proteins with a central role in innate adaptive immunity. As member of pattern recognition (PRRs), NLRs sense specific pathogen-associated molecular patterns, trigger numerous signaling pathways lead to the secretion various cytokines. In recent years, cumulative studies have revealed significant impacts gastrointestinal (GI) inflammatory diseases cancers. Deciphering mechanism NLR may provide new opportunities for development therapeutic strategies related GI This review presents structures NLRs, summarizes advances regarding cancers describes comprehensive based on this pathway.

Language: Английский

Citations

30

Intracellular Fusobacterium nucleatum infection increases METTL3-mediated m6A methylation to promote the metastasis of esophageal squamous cell carcinoma DOI Creative Commons
Songhe Guo, Fangfang Chen, Linfang Li

et al.

Journal of Advanced Research, Journal Year: 2023, Volume and Issue: 61, P. 165 - 178

Published: Aug. 22, 2023

The tumor-associated microbiota plays a vital role in cancer development. Accumulating evidence shows that Fusobacterium nucleatum (Fn) participates the progression of multiple tumor types. However, underlying mechanisms remain unclear. This study examined expression methyltransferase-like protein 3 (METTL3) during Fn infection and elucidated function pathway Fn-induced m6A methylation esophageal squamous cell carcinoma (ESCC). abundance patient tissues was determined by qPCR. Western blot, qRT-PCR, immunohistochemistry were performed to measure METTL3 cells tissues. evaluated vitro colony formation migration assays. MeRIP-qPCR determine relationship between c-Myc. In addition, half-lives genes are downstream with RNA stability enriched hepatocellular (HCC), breast (BRCA), ESCC, colorectal (CRC) positively associated ESCC could survive proliferation as well increase HCC, CRC, BRCA cells. Moreover, overexpression promoted proliferation, vivo vitro. Mechanistically, Intracellular increases transcription. c-Myc mRNA 3'-untranslated Region (3'-UTR) enhanced its YTH N6-Methyladenosine binding 1(YTHDF1)-dependent manner, which contributes induced metastasis. indicates intracellular promotes development metastasis, eradicating may be promising strategy for treating ESCC.

Language: Английский

Citations

26

Intratumor Fusobacterium nucleatum promotes the progression of pancreatic cancer via the CXCL1‐CXCR2 axis DOI Creative Commons
Masataka Hayashi, Naoki Ikenaga, Kohei Nakata

et al.

Cancer Science, Journal Year: 2023, Volume and Issue: 114(9), P. 3666 - 3678

Published: July 12, 2023

Intratumor bacteria modify the tumor immune microenvironment and influence outcomes of various tumors. Periodontal pathogen Fusobacterium nucleatum has been detected in pancreatic cancer tissues is associated with poor prognosis. However, it remains unclear how F. affects cancer. Here, we compared clinical features colonization tissues. was 15.5% (13/84) patients. The size significantly larger nucleatum-positive group than negative group. To clarify biological effect intratumor on progression, performed migration/invasion assays cytokine array analysis cells cocultured nucleatum. promoted CXCL1 secretion from cells, leading to progression through autocrine signaling. suppressed tumor-infiltrating CD8+ T by recruiting myeloid-derived suppressor (MDSCs) an nucleatum-injected subcutaneous mouse model, resulting progression. Furthermore, growth accelerated MDSC depletion or inhibitors. paracrine mechanisms CXCL1-CXCR2 axis. Blockade axis may be a novel therapeutic approach for patients

Language: Английский

Citations

25

Microbiota enterotoxigenic Bacteroides fragilis-secreted BFT-1 promotes breast cancer cell stemness and chemoresistance through its functional receptor NOD1 DOI Creative Commons
Wei Ma, Lu Zhang, Weilong Chen

et al.

Protein & Cell, Journal Year: 2024, Volume and Issue: 15(6), P. 419 - 440

Published: Feb. 29, 2024

Tumor-resident microbiota in breast cancer promotes initiation and malignant progression. However, targeting to improve the effects of therapy has not been investigated detail. Here, we evaluated composition tumors found that enterotoxigenic Bacteroides fragilis (ETBF) was highly enriched patients who did respond taxane-based neoadjuvant chemotherapy. ETBF, albeit at low biomass, secreted toxic protein BFT-1 promote cell stemness chemoresistance. Mechanistic studies showed directly bound NOD1 stabilized protein. expressed on ALDH+ stem cells (BCSCs) cooperated with GAK phosphorylate NUMB its lysosomal degradation, thereby activating NOTCH1-HEY1 signaling pathway increase BCSCs. inhibition ETBF clearance chemosensitivity by impairing

Language: Английский

Citations

14