Invasive Pathobionts Contribute to Colon Cancer Initiation by Counterbalancing Epithelial Antimicrobial Responses

Yu, Linda Chia‐Hui; Wei, Shu–Chen; Li, Yi-Hsuan; Lin, Po‐Chun; Chang, Xiaohong; Weng, Jui-Ping; Shue, Yin-Wen; Lai, Liang‐Chuan; Wang, Jann-Tay; Jeng, Yung‐Ming; Ni, Yen‐Hsuan

doi:10.1016/j.jcmgh.2021.08.007

Cited by 18 publications

(16 citation statements)

References 52 publications

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“…HtrA proteins have also been detected in H. influenzae , H. pylori , C. jejuni , and A. actinomycetemcomitans [10] . A recent study indicates that HtrA proteins in H. pylori are related to the risk of gastric cancer and a subsequent study suggested a time-specific host–microbe relationship probably exists in some gastrointestinal pathogens [61] , [62] . In Gram-negative bacteria, OMVs seem to be an effective means of translocation for virulence-associated HtrAs.…”

Section: The Versatile Roles Exhibited By Htra Proteins In Bacteriamentioning

confidence: 99%

Function, molecular mechanisms, and therapeutic potential of bacterial HtrA proteins: An evolving view

Song

Kang

et al. 2022

Computational and Structural Biotechnology Journal

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Members of the high temperature requirement A (HtrA) protein family are widely distributed amongst prokaryotic and eukaryotic species. HtrA proteins have ATP-independent dual chaperone-protease activity and mediate protein quality control. Emerging evidence indicates that HtrA family members are vital for establishing infections and bacterial survival under stress conditions. Bacterial HtrA proteins are increasingly thought of as important new targets for antibacterial drug development. Recent literature suggests that HtrA protein AlgW from Pseudomonas aeruginosa has distinct structural, functional, and regulatory characteristics. The novel dual-signal activation mechanism seen in AlgW is required to modulate stress and drug responses in bacteria, prompting us to review our understanding of the many HtrA proteins found in microorganisms. Here, we describe the distribution of HtrA gene orthologues in pathogenic bacteria, discuss their structure–function relationships, outline the molecular mechanisms exhibited by different bacterial HtrA proteins in bacteria under selective pressure, and review the significance of recently developed small molecule inhibitors targeting HtrA in pathogenic bacteria.

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Section: The Versatile Roles Exhibited By Htra Proteins In Bacteriamentioning

confidence: 99%

Function, molecular mechanisms, and therapeutic potential of bacterial HtrA proteins: An evolving view

Song

Kang

et al. 2022

Computational and Structural Biotechnology Journal

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“…The repression of autophagy by E. coli , in turn, led to increased generation of ROS and epithelial hyperproliferation. However, as the dysplasia tissue progressed, autophagy was upregulated to eradicate the pathogen, suggesting an E. coli -independent tumor growth in the late stage of CRC development [ 104 ]. In line with this, the only time window when antibiotic intervention exhibited a tumor-suppressive effect was in the middle stages of tumor development [ 104 ].…”

Section: Autophagy Coordinates Cellular Adaptation To Stress In the P...mentioning

confidence: 99%

From Intestinal Epithelial Homeostasis to Colorectal Cancer: Autophagy Regulation in Cellular Stress

et al. 2022

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The intestinal epithelium is continuously exposed to abundant stress stimuli, which relies on an evolutionarily conserved process, autophagy, to maintain its homeostasis by degrading and recycling unwanted and damaged intracellular substances. Otherwise, disruption of this balance will result in the development of a wide range of disorders, including colorectal cancer (CRC). Dysregulated autophagy is implicated in the regulation of cellular responses to stress during the development, progression, and treatment of CRC. However, experimental investigations addressing the impact of autophagy in different phases of CRC have generated conflicting results, showing that autophagy is context-dependently related to CRC. Thus, both inhibition and activation of autophagy have been proposed as therapeutic strategies against CRC. Here, we will discuss the multifaceted role of autophagy in intestinal homeostasis and CRC, which may provide insights for future research directions.

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“…The growth of colibactin E. coli is greatly enhanced with increased epithelial oxygenation, which is highly associated with tumorigenesis ( Cevallos et al., 2019 ). E. coli may also develop tumorigenicity in a healthy human gut over time and may contribute to CRC by adjusting host’s epithelial autophagy and oxidative stress response ( Yu et al., 2021 ). However, invasiveness of E. coli can be countered by PTPN2 gene which encodes for T-cell protein tyrosine phosphatase (TCPTP) ( Shawki et al., 2020 ).…”

Section: Gut Microbiota Dysbiosis In Eocrcmentioning

confidence: 99%

Gut Dysbiosis and Intestinal Barrier Dysfunction: Potential Explanation for Early-Onset Colorectal Cancer

Kendong

Ali

Nawawi

et al. 2021

Front. Cell. Infect. Microbiol.

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Colorectal cancer (CRC) is a heterogeneous disease that commonly affects individuals aged more than 50 years old globally. Regular colorectal screening, which is recommended for individuals aged 50 and above, has decreased the number of cancer death toll over the years. However, CRC incidence has increased among younger population (below 50 years old). Environmental factors, such as smoking, dietary factor, urbanization, sedentary lifestyle, and obesity, may contribute to the rising trend of early-onset colorectal cancer (EOCRC) because of the lack of genetic susceptibility. Research has focused on the role of gut microbiota and its interaction with epithelial barrier genes in sporadic CRC. Population with increased consumption of grain and vegetables showed high abundance of Prevotella, which reduces the risk of CRC. Microbes, such as Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli deteriorate in the intestinal barrier, which leads to the infiltration of inflammatory mediators and chemokines. Gut dysbiosis may also occur following inflammation as clearly observed in animal model. Both gut dysbiosis pre- or post-inflammatory process may cause major alteration in the morphology and functional properties of the gut tissue and explain the pathological outcome of EOCRC. The precise mechanism of disease progression from an early stage until cancer establishment is not fully understood. We hypothesized that gut dysbiosis, which may be influenced by environmental factors, may induce changes in the genome, metabolome, and immunome that could destruct the intestinal barrier function. Also, the possible underlying inflammation may give impact microbial community leading to disruption of physical and functional role of intestinal barrier. This review explains the potential role of the interaction among host factors, gut microenvironment, and gut microbiota, which may provide an answer to EOCRC.

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Invasive Pathobionts Contribute to Colon Cancer Initiation by Counterbalancing Epithelial Antimicrobial Responses

Cited by 18 publications

References 52 publications

Function, molecular mechanisms, and therapeutic potential of bacterial HtrA proteins: An evolving view

Function, molecular mechanisms, and therapeutic potential of bacterial HtrA proteins: An evolving view

From Intestinal Epithelial Homeostasis to Colorectal Cancer: Autophagy Regulation in Cellular Stress

Gut Dysbiosis and Intestinal Barrier Dysfunction: Potential Explanation for Early-Onset Colorectal Cancer

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