乳腺癌是全世界女性中最常见的恶性肿瘤之一。流行病学研究结果提示牙周病可能与乳腺癌有关,其中核梭杆菌被认为是重要的交叉参与者。在这项工作中,我们全面总结了核仁F.易位的已知机制,定植在乳腺肿瘤中,并促进致癌作用。具体来说,F.核仁通过乳腺-肠轴易位到乳腺组织,乳头直接接触,和血源性传播。随后,F.nucleatum利用融合杆菌自身转运蛋白2定植乳腺癌,并利用毒力因子融合杆菌粘附素A和脂多糖促进增殖。此外,由核仁F.诱导的基质金属蛋白酶-9上调不仅触发炎症反应,而且促进肿瘤促进微环境。除了促炎作用,F.核仁也可能参与肿瘤免疫逃避,这是通过毒力因子对T细胞上高度表达的免疫检查点受体的作用来实现的,自然杀伤细胞,和肿瘤浸润淋巴细胞.以乳腺癌为例,更多相关的研究可能会扩大我们目前对口腔微生物如何影响全身健康的认识。希望,深入研究这些机制,可以为更安全,更有效的乳腺癌生物靶向治疗提供新的策略.
Breast cancer is among the most prevalent malignancies in women worldwide. Epidemiological findings suggested that periodontal diseases may be associated with breast cancer, among which Fusobacterium nucleatum is considered an important cross-participant. In this work, we comprehensively summarize the known mechanisms of how F. nucleatum translocates to, colonizes in mammary tumors, and promotes the carcinogenesis. Specifically, F. nucleatum translocates to mammary tissue through the mammary-intestinal axis, direct nipple contact, and hematogenous transmission. Subsequently, F. nucleatum takes advantage of fusobacterium autotransporter protein 2 to colonize breast cancer and uses virulence factors fusobacterium adhesin A and lipopolysaccharide to promote proliferation. Moreover, the upregulated matrix metalloproteinase-9 induced by F. nucleatum does not only trigger the inflammatory response but also facilitates the tumor-promoting microenvironment. Aside from the pro-inflammatory effect, F. nucleatum may also be engaged in tumor immune evasion, which is achieved through the action of virulence factors on immune checkpoint receptors highly expressed on T cells, natural killer cells, and tumor-infiltrating lymphocytes. Taking breast cancer as an example, more relevant research studies may expand our current knowledge of how oral microbes affect systemic health. Hopefully, exploring these mechanisms in depth could provide new strategies for safer and more effective biologic and targeted therapies targeted at breast cancer.