introduction
Peptostreptococcus stomatis (P. stomatis), a common gram-positive anaerobic bacterium in the oral cavity, is often associated with periodontal diseases such as periodontitis and root canal infection. In recent years, with the progress of microbial research, it has been found that the abundance of P. stomatis is significantly higher in colorectal cancer patients than in healthy people, indicating that there is a slight association between the bacterium and cancer. However, so far, the mechanism of action of how this bacterium affects the occurrence and development of colorectal cancer has not been clarified. Therefore, it is of great clinical significance to explore the function of this bacterium and its impact on colorectal cancer.
2024年7月25日，香港中文大学黄子隽、于君教授团队在Cell Host & Microbe杂志在线发表了题为 Peptostreptococcus stomatis promotes colonic tumorigenesis and receptor tyrosine kinase inhibitor resistance by activating ERBB2-MAPK 的研究论文，通过多队列的横向分析，利用多种分子生物学技术及动物实验揭示了P. stomatis的功能。
This study showed that P. stomatis could promote cancer development in mouse models of spontaneous colorectal cancer (ApcMin/+ mice and azomethane/dextran oxide sulfate-treated mice) by inducing cell proliferation, inhibiting apoptosis, and damaging the intestinal mucosal barrier. Mechanistically, P. stomatis directly binds to the cancer cell surface receptor integrin α6/β4 through its surface protein fructose-1,6-bisphosphate aldolase (FBA), thereby causing the aberrant activation of the oncogenic pathway ERBB2-MEK-ERK-p90. In vitro experiments showed that inhibition of the interaction between FBA-integrin α6/β4 could eliminate the activation of oncogenic signals and the carcinogenic effect caused by the bacterium. In subsequent cell and animal experiments, the study found that P. The activation of ERBB2 signaling caused by stomatis can bypass the antagonism of EGFR inhibitors (cetuximab, erlotinib) on tyrosine kinase receptors, and the bacterium can weaken the therapeutic effect of BRAF inhibitors (vemurafenib), which in turn leads to drug resistance in patients with KRAS wild-type or BRAF-mutant colorectal cancer, which means that the bacterium has a non-negligible impact on the treatment of cancer patients.
In summary, the study confirmed that the pathogenic bacterium P. Stomatis is involved in regulating the occurrence, development and therapeutic effect of colorectal cancer, which is a good way to explore the treatment of colorectal cancer in the future. The clinical intervention of stomatis lays the groundwork.
模式图（Credit: Cell Host & Microbe）
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https://authors.elsevier.com/sd/article/S1931-3128(24)00254-3
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