Iron accelerates Fusobacterium nucleatum–induced CCL8 expression in macrophages and is associated with colorectal cancer progression

Yamane, Teiichi; Kanamori, Yohei; Shinmoto, Hiroshi; Yano, Hiromichi; Nita, Akihiro; Ohta, Yudai; Hinokuma, Hironori; Maeda, Ayato; Iwai, Akiko; Matsumoto, Takashi; Shimoda, Mayuko; Niimura, Mayumi; Usuki, Shingo; Yasuda-Yoshihara, Noriko; Niwa, Masato; Baba, Yoshifumi; Ishimoto, Takatsugu; Komohara, Yoshihiro; Sawa, Tomohiro; Hirayama, Tasuku; Baba, Hideo; Moroishi, Toshiro

doi:10.1172/jci.insight.156802

Cited by 4 publications

(4 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was found that there was an obvious increase in HCT116 cell proliferation following a 48 h incubation with F. nucleatum at a concentration of 1:1000 (Figure 3f), which is consistent with previous reports. 16,51,52 Then, F. nucleatuminfected HCT116 cells were used to evaluate the effect of SDT combined with an antibacterial. As shown in Figure 3g, after US irradiation, Au@BSA-CuPpIX exhibited a more obvious inhibitory effect on cell viability than Au@BSA-PpIX, suggesting that the sonotoxicity of Au@BSA-CuPpIX for F. nucleatum-infected tumor cells was stronger than that of Au@ BSA-PpIX, which could be attributed to the stronger antibacterial ability of Au@BSA-CuPpIX to eliminate F. nucleatum.…”

Section: Resultsmentioning

confidence: 99%

“…For in vivo lung metastasis models, 6-week-old male BALB/c nude mice were constructed as previously reported. , Luciferase-transfected HCT-116 cells were incubated with F. nucleatum (1:1000) for 48 h, and the cell resuspension solution was injected via the tail vein (10 6 cells, 100 μL per mouse). Mice were injected with PBS (100 μL per mouse), Au@BSA-CuPpIX (10 mg/kg), and Au@BSA-PpIX (10 mg/kg).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Modulation of Intratumoral Fusobacterium nucleatum to Enhance Sonodynamic Therapy for Colorectal Cancer with Reduced Phototoxic Skin Injury

Qu,

Yin,

Pei

et al. 2023

ACS Nano

View full text Add to dashboard Cite

Intratumoral pathogens can contribute to cancer progression and affect therapeutic response. Fusobacterium nucleatum, a core pathogen of colorectal cancer (CRC), is an important cause of low therapeutic efficacy and metastasis. Thus, the modulation of intratumoral pathogens may provide a target for cancer therapy and metastasis inhibition. Herein, we propose an intratumoral F. nucleatum-modulating strategy for enhancing the therapeutic efficacy of CRC and inhibiting lung metastasis by designing an antibacterial nanoplatform (Au@BSA-CuPpIX), which produced reactive oxygen species (ROS) under ultrasound and exhibited strong antibacterial activity. Importantly, Au@BSA-CuPpIX reduced the levels of apoptosis-inhibiting proteins by inhibiting intratumoral F. nucleatum, thereby enhancing ROS-induced apoptosis. In vivo results demonstrated that Au@BSA-CuPpIX effectively eliminated F. nucleatum to enhance the therapeutic efficacy of sonodynamic therapy (SDT) for orthotopic CRC and inhibit lung metastasis. Notably, entrapped gold nanoparticles reduced the phototoxicity of metalloporphyrin accumulated in the skin during tumor treatment, preventing severe inflammation and damage to the skin. Therefore, this study proposes a strategy for the elimination of F. nucleatum in CRC to enhance the therapeutic effect of SDT, thus providing a promising paradigm for improving cancer treatment with fewer toxic side effects and promoting the clinical translational potential of SDT.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Modulation of Intratumoral Fusobacterium nucleatum to Enhance Sonodynamic Therapy for Colorectal Cancer with Reduced Phototoxic Skin Injury

Qu,

Yin,

Pei

et al. 2023

ACS Nano

View full text Add to dashboard Cite

show abstract

“…Fusobacterium nucleatum was reported to promote METTL3‐mediated microRNA‐4717‐3p maturation 50 . Supporting evidence from research showed the pro‐EMT activity of F. nucleatum in CRC cell lines 51–53 . Zheng et al 54 reported that adverse F. nucleatum overpopulation in patients and mice suppressed the beneficial C. butyricum population.…”

Section: Discussionmentioning

confidence: 96%

“…50 Supporting evidence from research showed the pro-EMT activity of F. nucleatum in CRC cell lines. [51][52][53] Zheng et al 54 reported that adverse F. nucleatum overpopulation in patients and mice suppressed the beneficial C. butyricum population. Furthermore, Zong et al 55 revealed that enterotoxigenic Escherichia coli infection can promote enteric defensin expression through the FOXO6-METTL3-m 6 A-GPR161 signaling axis.…”

Section: Clostridium Butyricum Inhibited Mettl3 and Emt Process By Up...mentioning

confidence: 99%

Clostridium butyricum inhibits epithelial–mesenchymal transition of intestinal carcinogenesis through downregulating METTL3

Zhang

Dong

et al. 2023

Cancer Science

View full text Add to dashboard Cite

Colorectal cancer (CRC) is related to gut microbiota dysbiosis, especially butyrateproducing bacteria reduction. Our previous study suggested that administration of Clostridium butyricum, a butyrate-producing bacterium, exerts a crucial effect against CRC, however the potential mechanism is not clear. We first found that methyltransferase-like 3 (METTL3) showed a positive correlation with proliferation, epithelial-mesenchymal transition (EMT), DNA repair, metastasis, and invasion in a database analysis. The expression of METTL3 gradually increased from human normal colon tissue, to adenoma, and carcinoma, and was positively correlated with Ecadherin and CD34 levels. Overexpression of METTL3 promoted the proliferation, migration, and invasion of CRC cells and induced vasculogenic mimicry (VM) formation. Clostridium butyricum could downregulate METTL3 expression in CRC cells and decrease the expression of vimentin and vascular endothelial growth factor receptor 2 to reduce EMT and VM formation. Clostridium butyricum alleviated the pro-oncogenic effect of METTL3 overexpressing plasmid in CRC cells. The anti-EMT effect on METTL3 reduction of C. butyricum could be blunted by knocking down Gprotein coupled receptor 43. Moreover, C. butyricum prevented EMT and VM and inhibited tumor metastasis in nude mice. Accordingly, C. butyricum could inhibit EMT and VM formation of intestinal carcinogenesis through downregulating METTL3.These findings broaden our understanding of probiotics supplement in CRC prevention and treatment.

show abstract

Butyrate Prevents the Pathogenic Anemia‐Inflammation Circuit by Facilitating Macrophage Iron Export

Xiao,

Cai,

Zhang

et al. 2024

Advanced Science

View full text Add to dashboard Cite

Most patients with inflammatory bowel disease (IBD) develop anemia, which is attributed to the dysregulation of iron metabolism. Reciprocally, impaired iron homeostasis also aggravates inflammation. How this iron‐mediated, pathogenic anemia‐inflammation crosstalk is regulated in the gut remains elusive. Herein, it is for the first time revealed that anemic IBD patients exhibit impaired production of short‐chain fatty acids (SCFAs), particularly butyrate. Butyrate supplementation restores iron metabolism in multiple anemia models. Mechanistically, butyrate upregulates ferroportin (FPN) expression in macrophages by reducing the enrichment of histone deacetylase (HDAC) at the Slc40a1 promoter, thereby facilitating iron export. By preventing iron sequestration, butyrate not only mitigates colitis‐induced anemia but also reduces TNF‐α production in macrophages. Consistently, macrophage‐conditional FPN knockout mice exhibit more severe anemia and inflammation. Finally, it is revealed that macrophage iron overload impairs the therapeutic effectiveness of anti‐TNF‐α antibodies in colitis, which can be reversed by butyrate supplementation. Hence, this study uncovers the pivotal role of butyrate in preventing the pathogenic circuit between anemia and inflammation.

show abstract

Iron accelerates Fusobacterium nucleatum–induced CCL8 expression in macrophages and is associated with colorectal cancer progression

Cited by 4 publications

References 45 publications

Modulation of Intratumoral Fusobacterium nucleatum to Enhance Sonodynamic Therapy for Colorectal Cancer with Reduced Phototoxic Skin Injury

Modulation of Intratumoral Fusobacterium nucleatum to Enhance Sonodynamic Therapy for Colorectal Cancer with Reduced Phototoxic Skin Injury

Clostridium butyricum inhibits epithelial–mesenchymal transition of intestinal carcinogenesis through downregulating METTL3

Butyrate Prevents the Pathogenic Anemia‐Inflammation Circuit by Facilitating Macrophage Iron Export

Contact Info

Product

Resources

About