<i>Fusobacterium nucleatum</i> promotes colorectal cancer metastasis by modulating <i>KRT7-AS</i>/KRT7

Chen, Shujie; Su, Tingting; Zhang, Ying; Lee, Allen; He, Jiamin; Ge, Qiwei; Wang, Lan; Si, Jianmin; Zhuo, Wei; Wang, Liangjing

doi:10.1080/19490976.2019.1695494

Cited by 139 publications

(106 citation statements)

References 35 publications

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“…Gut bacterial dysbiosis is commonly seen in patients with CRC. Although in literature there are discrepancies regarding the bacterial profiles associated with CRC, higher abundance of Fusobacterium is one of the most frequent observations associated with CRC status (32,33). In line with previous studies, we observed significant differences (p=0.01) in the presence of Fusobacterium among CRC patients and controls.…”

Section: Discussionsupporting

confidence: 89%

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Gut Microbiota and Host Gene Mutations in Colorectal Cancer Patients and Controls of Iranian and Finnish Origin

Sarhadi¹,

Lahti

Saberi³

et al. 2020

Anticancer Res

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Background/Aim: Gut microbiota plays an important role in colorectal cancer (CRC) and its composition in CRC patients can be influenced by ethnicity and tumour genomics. Herein, the aim was to study the possible associations of ethnicity and gene mutations with the gut microbiota in CRC patients. Materials and Methods: Bacterial composition in stool samples of 83 CRC patients and 60 controls from Iran and Finland was studied by 16S rRNA gene sequencing. The association of gut microbiota composition with CRC, host mutations in KRAS, NRAS and TP53, and ethnicity analysed. Results: Beta diversity analysis indicated significant differences between the Iranian and Finnish gut microbiota composition, in both controls and patients' groups. The Iranian controls had higher abundance of Prevotella and lower abundance of Bacteroides compared to the Finnish controls, while the Finnish patients had higher abundance of Clostridium compared to Iranian patients. Abundance of Ruminococcus was higher in patients compared to the controls. Higher abundances of Herbaspirillum, Catenibacterium and lower abundances of Barnesiella were associated with mutations in NRAS, TP53, and RAS respectively. Conclusion: A possible link of host gene mutations with gut bacterial composition is suggested. The gut microbiota plays an integral role in the regulation of different gastrointestinal functions. There is increasing evidence that the gut microbiota not only contributes to the initiation and progression of colorectal cancer (CRC) but also influences the host response to cancer treatment, especially chemo-and immunotherapy (1). In addition to its regional effect in the gastrointestinal tract, the gut microbiota also affects distant organs via its role in shaping the immune system and host metabolism (2). Diet, lifestyle and ethnicity are among the main determinants of microbiota composition, and changes in diet associated with a modern lifestyle have been linked to microbiota-mediated cancer risk (3). The host genetic variation is also known to effect bacterial composition (4), although this area has not been investigated extensively. The host genetics is reported to strongly influence the abundance of gut Christensenellaceae (5), the bacteria associated with low body mass index. The Bifidobacterium abundance has been linked with a variation in the lactose tolerance gene LCT loci (6, 7). On the other hand, tumour genome is reported to be a factor modulating colonization of certain bacteria around colorectal tumour tissue (8, 9). A high abundance of Fusobacterium has been reported to be associated with CpG island methylator phenotype (CIMP), microsatellite instability (MSI) and mutations in CHD7/8 (10). However, the associations between tumour mutations and gut microbiota composition remain poorly understood. The association of the gut microbiota composition with different disease states makes them useful as potential diagnostic markers of health and disease (11). Recent largescale studies have however demonstrated that ethnicity (12) and geogra...

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Section: Discussionsupporting

confidence: 89%

“…In line with previous studies, we observed significant differences (p=0.01) in the presence of Fusobacterium among CRC patients and controls. Fusobacterium has been found to be strongly associated with CRC (32) and involved in metastasis of CRC (33).…”

Section: Discussionmentioning

confidence: 99%

Gut Microbiota and Host Gene Mutations in Colorectal Cancer Patients and Controls of Iranian and Finnish Origin

Sarhadi¹,

Lahti

Saberi³

et al. 2020

Anticancer Res

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“…In the intestinal tumor microenvironment, F. nucleatum selectively expanded myeloid-derived immune cells but not lymphoid immune cells, leading to tumor progression [ 37 ]. Moreover, F. nucleatum promotes metastasis of CRC by modulating KRT7-AS / KRT7 [ 38 ].…”

Section: F Nucleatum and Cancermentioning

confidence: 99%

Involvement of Fusobacterium Species in Oral Cancer Progression: A Literature Review Including Other Types of Cancer

Fujiwara

Kitamura

Yoshida

et al. 2020

IJMS

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Chronic inflammation caused by infections has been suggested to be one of the most important cause of cancers. It has recently been shown that there is correlation between intestinal bacteria and cancer development including metastasis. As over 700 bacterial species exist in an oral cavity, it has been concerning that bacterial infection may cause oral cancer. However, the role of bacteria regarding tumorigenesis of oral cancer remains unclear. Several papers have shown that Fusobacterium species deriving the oral cavities, especially, play a crucial role for the development of colorectal and esophageal cancer. F. nucleatum is a well-known oral bacterium involved in formation of typical dental plaque on human teeth and causing periodontal diseases. The greatest characteristic of F. nucleatum is its ability to adhere to various bacteria and host cells. Interestingly, F. nucleatum is frequently detected in oral cancer tissues. Moreover, detection of F. nucleatum is correlated with the clinical stage of oral cancer. Although the detailed mechanism is still unclear, Fusobacterium species have been suggested to be associated with cell adhesion, tumorigenesis, epithelial-to-mesenchymal transition, inflammasomes, cell cycle, etc. in oral cancer. In this review, we introduce the reports focused on the association of Fusobacterium species with cancer development and progression including oral, esophageal, and colon cancers.

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“…Genomic studies furnished the earliest evidence that F. nucleatum is prevalent in CRC (Castellarin et al, 2012;Kostic et al, 2012). These were followed by reports indicating that F. nucleatum plays a role in CRC development (Castellarin et al, 2012;Kostic et al, 2012Kostic et al, , 2013Bullman et al, 2017), metastasis (Li et al, 2016;Bullman et al, 2017;Casasanta et al, 2020;Chen et al, 2020), and disease outcome (Mima et al, 2016;Yu et al, 2017;Brennan and Garrett, 2018). Mechanisms by which F. nucleatum promotes tumor progression include generating a proinflammatory tumor-promoting microenvironment (Kostic et al, 2013) and accelerating proliferation of colon cancer cells through activation of Wnt/beta-catenin signaling (Rubinstein et al, 2013(Rubinstein et al, , 2019Wu et al, 2018b) and through TLR4-activated signaling to NF-κB (Yang et al, 2017;Wu et al, 2018b).…”

Section: Introductionmentioning

confidence: 99%

Colon Cancer-Associated Fusobacterium nucleatum May Originate From the Oral Cavity and Reach Colon Tumors via the Circulatory System

Abed

Maalouf

Manson

et al. 2020

Front. Cell. Infect. Microbiol.

131

128

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Fusobacterium nucleatum is a common oral bacterium that is enriched in colorectal adenomas and adenocarcinomas (CRC). In humans, high fusobacterial CRC abundance is associated with chemoresistance and poor prognosis. In animal models, fusobacteria accelerate CRC progression. Targeting F. nucleatum may reduce fusobacteria cancer progression and therefore determining the origin of CRC F. nucleatum and the route by which it reaches colon tumors is of biologic and therapeutic importance. Arbitrarily primed PCR performed previously on matched same-patients CRC and saliva F. nucleatum isolates, suggested that CRC F. nucleatum may originate from the oral cavity. However, the origin of CRC fusobacteria as well as the route of their arrival to the tumor have not been well-established. Herein, we performed and analyzed whole genome sequencing of paired, same-patient oral, and CRC F. nucleatum isolates and confirmed that CRC-fusobacteria originate from the oral microbial reservoir. Oral fusobacteria may translocate to CRC by descending via the digestive tract or using the hematogenous route during frequent transient bacteremia caused by chewing, daily hygiene activities, or dental procedures. Using the orthotropic CT26 mouse model we previously showed that IV injected F. nucleatum colonize CRC. Here, we compared CRC colonization by gavage vs. intravenous inoculated F. nucleatum in the MC38 and CT26 mouse orthotropic CRC models. Under the tested conditions, hematogenous fusobacteria were more successful in CRC colonization than gavaged ones. Our results therefore provide evidence that the hematogenous route may be the preferred way by which oral fusobacteria reach colon tumors.

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Fusobacterium nucleatum promotes colorectal cancer metastasis by modulating KRT7-AS/KRT7

Cited by 139 publications

References 35 publications

Gut Microbiota and Host Gene Mutations in Colorectal Cancer Patients and Controls of Iranian and Finnish Origin

Gut Microbiota and Host Gene Mutations in Colorectal Cancer Patients and Controls of Iranian and Finnish Origin

Involvement of Fusobacterium Species in Oral Cancer Progression: A Literature Review Including Other Types of Cancer

Colon Cancer-Associated Fusobacterium nucleatum May Originate From the Oral Cavity and Reach Colon Tumors via the Circulatory System

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