Nature Communications
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2025
·Vol. 16
·期 1
·1-19
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IF 15.7
Qi Houbao,Gao Haiting,Li Meihui,Sun Tianyong,Gu Xiufeng,Wei Li,Zhi Mengfan,Li Zixuan,Fu Dachuan,Liu Yiran,Wei Ziyi,Dou Yu,Feng Qiang
Parvimonas micra ( P. micra ), an opportunistic oral pathogen associated with multiple cancers, has limited research on its role in oral squamous cell carcinoma (OSCC). This study shows that P. micra is enriched in OSCC tissues and positively correlated with tumor metastasis and stages. P. micra infection promotes OSCC metastasis by inducing hypoxia/HIF-1α, glycolysis, and autophagy. Mechanistically, P. micra surface protein TmpC binds to CKAP4, a receptor overexpressed in OSCC, facilitating bacterial attachment and invasion. This interaction activates HIF-1α and autophagy via CKAP4-RanBP2 and CKAP4-NBR1 pathways, driving metastasis. Targeting CKAP4 with masitinib or antibodies impairs P. micra attachment and abolishes P. micra -promoted OSCC metastasis in vitro and in vivo. Together, our findings identify P. micra as a pathogen that promotes OSCC metastasis and highlight that TmpC-CKAP4 interaction could be a potential therapeutic target for OSCC.
研究领域:
肿瘤学
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微生物学
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分子生物学
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癌症研究
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PubMed
高影响因子
EBioMedicine
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2026
·
IF 11.2
Zixuan Li,Pingping Wang,Haiting Gao,Mengfan Zhi,Xiufeng Gu,Tianyong Sun,Yushang Wang,Song Shen,Xiaomei Ma,Xiaoli Ji,Xiumei Zhang,Dongxu Liu,Qiang Feng
Background Periodontitis poses a significant threat to human oral health, and microorganisms serving as the initiating factor in its pathogenesis. Parvimonas micra ( P. micra ), a Gram-positive anaerobic bacterium prevalent within the oral cavities of patients with periodontitis, remains underexplored in terms of its full contribution to periodontitis pathogenesis. Methods 16S rRNA sequencing was performed on human gingival crevicular fluid samples, whilst micro-CT was used in experimental rat models to assess the impact of P. micra on periodontitis progression. Single-cell RNA sequencing was employed to examine dynamic alterations in rat periodontal cell composition and the enrichment of gene pathways during P. micra infection. Finally, His pull-down assay combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to identify key virulence factors of P. micra and host cell receptors. Findings In this study, we examined the abundance of P. micra in gingival crevicular fluid and validated its pathogenic potential in vivo . Single-cell RNA sequencing revealed that P. micra disrupted the periodontal immune and mineralisation microenvironment. Further investigation showed that P. micra manipulated its surface adhesins to bind receptors on periodontal ligament stem cells, activating the intracellular NF-κB and ERK1/2 signalling pathways and impairing osteogenic activity. Finally, we identified a mechanism by which P. micra employed a surface protein to evade autophagic clearance, thereby facilitating immune escape. Interpretation This study identifies P. micra as a pivotal periodontal pathogen, and the elucidation of its molecular mechanisms provides potential therapeutic targets for periodontitis and related systemic conditions. Funding This work was supported by the National Natural Science Foundation of China (No. 82270980, 82071122), Noncommunicable Chronic Diseases-National Science and Technology Major Project (2023ZD0501400), Taishan TePin Scientist Project of Shandong Province (tstp20250546), the Natural Science Foundation of Jiangsu Province (No. BK20240268), High-Level Hospital Construction Project of Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University (No. 0024C035), Shandong Provincial Key Research and Development Program (Competitive Innovation Platform, 2025CXPT042), the Major Innovation Projects in Shandong Province (No. 2021SFGC0502), and the Shandong Province Key Research and Development Program (No. 2021ZDSYS18).
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高影响因子
CELL
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2024
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IF 45.5
Kaili Fu,Alvin Ho Kwan Cheung,Chi Chun Wong,Weixin Liu,Yunfei Zhou,Feixue Wang,Pingmei Huang,Kai Yuan,Olabisi Oluwabukola Coker,Yasi Pan,Danyu Chen,Nga Man Lam,Mengxue Gao,Xiang Zhang,He Huang,Ka Fai To,Joseph Jao Yiu Sung,Jun Yu
Summary Streptococcus anginosus ( S. anginosus ) was enriched in the gastric mucosa of patients with gastric cancer (GC). Here, we show that S. anginosus colonized the mouse stomach and induced acute gastritis. S. anginosus infection spontaneously induced progressive chronic gastritis, parietal cell atrophy, mucinous metaplasia, and dysplasia in conventional mice, and the findings were confirmed in germ-free mice. In addition, S. anginosus accelerated GC progression in carcinogen-induced gastric tumorigenesis and YTN16 GC cell allografts. Consistently, S. anginosus disrupted gastric barrier function, promoted cell proliferation, and inhibited apoptosis. Mechanistically, we identified an S. anginosus surface protein, TMPC, that interacts with Annexin A2 (ANXA2) receptor on gastric epithelial cells. Interaction of TMPC with ANXA2 mediated attachment and colonization of S. anginosus and induced mitogen-activated protein kinase (MAPK) activation. ANXA2 knockout abrogated the induction of MAPK by S. anginosus . Thus, this study reveals S. anginosus as a pathogen that promotes gastric tumorigenesis via direct interactions with gastric epithelial cells in the TMPC-ANXA2-MAPK axis.
研究领域:
微生物学
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肿瘤学
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胃肠病学
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分子生物学
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PubMed
高影响因子
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