Fusobacterium nucleatum-Induced Impairment of Autophagic Flux Enhances the Expression of Proinflammatory Cytokines via ROS in Caco-2 Cells

Tang, Bin; Wang, Kun; Jia, Yin-ping; Zhu, Pan; Yao, Fang; Zhang, Zhu-jun; Mao, Xuhu; Li, Qian; Zeng, Da‐Wu

doi:10.1371/journal.pone.0165701

Cited by 44 publications

(36 citation statements)

References 37 publications

(33 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In an in vitro experimental study, 61 KRAS mutation in colorectal cancer appeared to attenuate tumor SQSTM1 expression level, and we observed the similar trend. In another in vitro experimental study, 62 F. nucleatum appeared to induce impairment of autophagic activity of host cells; however, our current data do not support such negative effects of F. nucleatum on autophagic activity of tumor cells. Further studies are needed to determine the associations of tumor SQSTM1 expression with clinical, pathological and molecular characteristics of colorectal cancer.…”

Section: Discussioncontrasting

confidence: 99%

Tumor SQSTM1 (p62) expression and T cells in colorectal cancer

et al. 2017

View full text Add to dashboard Cite

Evidence suggests that activation of autophagy in neoplastic cells potentiates antitumor immunity through cross-presentation of tumor-associated antigens to T cells and release of immune mediators. The SQSTM1 (sequestosome 1, p62) protein is degraded by activated autophagy, and might enhance immune response to tumor cells. We hypothesized that tumor SQSTM1 expression level might be inversely associated with T-cell densities in colorectal carcinoma tissue. We evaluated tumor SQSTM1 expression by immunohistochemistry in 601 rectal and colon cancer cases within the Nurses' Health Study and Health Professionals Follow-up Study. Ordinal logistic regression analyses were conducted to assess the association of tumor SQSTM1 expression with CD3, or FOXP3 C cell density in tumor tissue, controlling for potential confounders, including tumor status of microsatellite instability, CpG island methylator phenotype, long interspersed nucleotide element-1 methylation level, and KRAS, BRAF, and PIK3CA mutations. Tumor SQSTM1 expression level was inversely associated with FOXP3 C cell density (p trend D 0.006), but not with CD3C , CD8 C , or CD45RO C cell density (with the adjusted a level of 0.01 for multiple hypothesis testing). For a unit increase in quartile categories of FOXP3 C cell density, multivariable odds ratios were 0.66 [95% confidence interval (CI), 0.45-0.98] for intermediate-level SQSTM1 expression, and 0.55 (95% CI, 0.36-0.83) for high-level SQSTM1 expression, compared with low-level SQSTM1 expression. Tumor SQSTM1 expression is inversely associated with FOXP3 C cell density in colorectal cancer tissue, suggesting a possible role of SQSTM1-expressing carcinoma cells on regulatory T cells in the tumor microenvironment.Abbreviations: ATP, adenosine triphosphate; CI, confidence interval; CIMP, CpG island methylator phenotype; FFPE, formalin-fixed paraffin-embedded; LINE-1, long interspersed nucleotide element-1; MSI, microsatellite instability;

show abstract

Section: Discussioncontrasting

confidence: 99%

Tumor SQSTM1 (p62) expression and T cells in colorectal cancer

et al. 2017

View full text Add to dashboard Cite

show abstract

“…37 F nucleatum infection was reported to activate autophagy, inducing the resistance of culture cells to chemotherapeutic drugs. 38 In contrast, Tang et al 39 showed that F nucleatum blocks the autophagic process at the autophagosome-lysosome fusion stage, and this promotes the proinflammatory response in the human Caco-2 CRC cell line. Our study, therefore, contributes to a better understanding of the role of autophagy in the infectious etiology of CRC, an area that is still little explored.…”

Section: Discussionmentioning

confidence: 95%

Autophagy of Intestinal Epithelial Cells Inhibits Colorectal Carcinogenesis Induced by Colibactin-Producing Escherichia coli in Apc Mice

et al. 2020

View full text Add to dashboard Cite

BASIC AND TRANSLATIONAL AT increase in mean histologic score, than infected Apc Min/þ mice. Increased levels of Il6, Tnf, and Cxcl1 mRNAs, decreased level of Il10 mRNA, and increased markers of DNA double-strand breaks and proliferation were observed in the colonic mucosa of 11G5-infected Apc Min/þ /Atg16l1 DIEC mice vs 11G5-infected Apc Min/þ mice. CONCLUSION: Infection of IECs and susceptible mice with CoPEC promotes autophagy, which is required to prevent colorectal tumorigenesis. Loss of ATG16L1 from IECs increases markers of inflammation, DNA damage, and cell proliferation and increases colorectal tumorigenesis in 11G5-infected Apc Min/þ mice. These findings indicate the importance of autophagy in response to CoPEC infection, and strategies to induce autophagy might be developed for patients with CRC and CoPEC colonization.

show abstract

“…Infection of Helicobacter pylori in gastric cells also induces inflammation that causes aberrant DNA methylation (48). In fact, when human cell lines were co-cultured with Fn in vitro, expression of pro-inflammatory genes including TNF, IL8, and IL1β as well as ROS was induced (49,50). Kostic et al analyzed transcriptome sequences from 133 cases of CRC in the TCGA data set (26) to identify the genes associated with Fusobacterium species infections (5).…”

Section: Possible Explanation Of Why Fusobacterium Infection Is Assocmentioning

confidence: 99%

<i>Fusobacterium nucleatum</i> Infection in Colorectal Cancer: Linking Inflammation, DNA Mismatch Repair and Genetic and Epigenetic Alterations

Koi

Okita

Carethers

2018

J Anus Rectum Colon

View full text Add to dashboard Cite

It has been recently reported that the population of Fusobacterium, particularly Fusobacterium nucleatum (Fn), is overrepresented in colorectal cancers and adenomas. The promoting effects of Fn infection on adenoma and/or carcinoma formation have been shown in ApcMin/+mice. Characteristics of Fn-associated CRC were identified through studies using human CRC cohorts, and include right-sided colon location, CpG island methylation phenotype-high (CIMP-H), high level of microsatellite instability (MSI-H), and poor patient prognosis. A subset of Fn-associated CRC exhibits a low level of microsatellite instability (MSI-L) and elevated microsatellite alterations in selected tetra-nucleotide repeats (EMAST) induced by translocation of MSH3 from the nucleus to the cytoplasm in response to oxidative DNA damage or inflammatory signals. The association between CIMP/MSI-H and Fn-infection can be explained by the role of the mismatch repair (MMR) protein complex formed between MSH2 and MSH6 (MutSα) to repair aberrant bases generated by ROS to form 7,8-dihydro-8-oxo-guanine (8-oxoG). Clustered 8-oxoGs formed at CpG-rich regions including promoters by ROS is refractory to base excision repair (BER). Under these conditions, MutSα initiates repair in cooperation with DNA methyltransferases (DNMTs) and the polycomb repressive complex 4 (PRC4). DNMTs at damaged sites methylate CpG islands to repress transcription of target genes and promote repair reactions. Thus, continuous generation of ROS through chronic Fn infection may initiate 1) CIMP-positive adenoma and carcinoma in an MSH2/MSH6-dependent manner, and/or 2) MSI-L/EMAST CRC in an MSH3-dependent manner. The poor prognosis of Fn-associated CRC can be explained by Fn-induced immune-evasion and/or chemo-resistance.

show abstract

Fusobacterium nucleatum-Induced Impairment of Autophagic Flux Enhances the Expression of Proinflammatory Cytokines via ROS in Caco-2 Cells

Cited by 44 publications

References 37 publications

Tumor SQSTM1 (p62) expression and T cells in colorectal cancer

Tumor SQSTM1 (p62) expression and T cells in colorectal cancer

Autophagy of Intestinal Epithelial Cells Inhibits Colorectal Carcinogenesis Induced by Colibactin-Producing Escherichia coli in Apc Mice

<i>Fusobacterium nucleatum</i> Infection in Colorectal Cancer: Linking Inflammation, DNA Mismatch Repair and Genetic and Epigenetic Alterations

Contact Info

Product

Resources

About