2. Academic Validation
  3. Colonization by Porphyromonas gingivalis in cervical squamous cell carcinomas promotes metastasis through FimA/CD151/ITGB1 signaling

Colonization by Porphyromonas gingivalis in cervical squamous cell carcinomas promotes metastasis through FimA/CD151/ITGB1 signaling

  • J Transl Med. 2025 Oct 24;23(1):1166. doi: 10.1186/s12967-025-06928-y.
Xiuting Huang # 1,  Yuan Zhuang # 2,  Rui Wang # 1,  Jing Qu # 3,  Yuanyang Tan # 1,  Liang Li 4,  Wenjun Pan 1,  Huilong Nie 2,  Kefeng Li 5,  Yujing Lin 6,  Liutong Yi 6,  Xiaoyu Feng 1,  Huimin Lan 1,  Guangxue Wang 7,  Xiantao Zeng 8,  Zhenqi Jiang 9,  De-Yun Wang 10,  Yongkang Qiao 11,  Yan Yan 12
Affiliations

Affiliations

  • 1 Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, 519000, China.
  • 2 Department of Gynecology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, 519000, China.
  • 3 Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China.
  • 4 Department of Pharmacology, Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, China.
  • 5 Faculty of Applied Sciences, Macao Polytechnic University, Macau, 999078, SAR , China.
  • 6 Department of Pathology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, 519000, China.
  • 7 Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
  • 8 Center for Evidence‑Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
  • 9 School of Medical Technology, School of Life Science, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 100081, China.
  • 10 Department of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore, 119228, Singapore. entwdy@nus.edu.sg.
  • 11 Centre for Biological Science and Technology, Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, Guangdong Zhuhai-Macao Joint Biotech Laboratory, Department of Biology, Faculty of Arts and Sciences, Beijing Normal University, Zhuhai , 519087, Guangdong, China. ykqiao@bnu.edu.cn.
  • 12 Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, 519000, China. yanyan35@mail.sysu.edu.cn.
  • # Contributed equally.
PMID: 41136985 DOI: 10.1186/s12967-025-06928-y
Abstract

Background: Cervicovaginal microbiota dysbiosis has been implicated in the progression of cervical Cancer. Recent studies have reported an increased abundance of Porphyromonas species in the vaginal microbiota of cervical Cancer patients. Porphyromonas gingivalis (P. gingivalis), a key periodontal pathogen, has been associated with adverse pregnancy outcomes and Bacterial vaginosis; however, its potential role in the progression of cervical squamous cell carcinoma (CSCC) remains largely unexplored.

Methods: We employed immunohistochemistry (IHC), 16S rRNA fluorescence in situ hybridization (FISH), and immunofluorescence to detect P. gingivalis in CSCC tissues. The association between P. gingivalis colonization and CSCC patient survival outcomes was assessed. Transwell and wound healing assays were used to assess the migration and invasion abilities of CSCC cells. In vivo xenograft mouse models were established to evaluate the impact of P. gingivalis on tumor growth and metastasis. Pull-down assays were employed to investigate interactions between the P. gingivalis fimbrial protein FimA and host cell membrane proteins. RNA Sequencing and Western blotting were utilized to identify signaling pathways activated by P. gingivalis in host cells.

Results: Porphyromonas gingivalis was detected immunohistochemically in 63% of CSCC tumor tissues, with significantly higher colonization in tumors compared to adjacent nontumor tissues (P < 0.0001). The presence of P. gingivalis was significantly associated with advanced tumor stage (P < 0.01), distant metastasis (P < 0.05), lymph node metastasis (P < 0.01), and poor survival outcomes (P = 0.0257, HR = 3.167) in CSCC patients. P. gingivalis preferentially adhered to CSCC cells and promoted cell migration and invasion. In this study, animal models revealed that P. gingivalis promoted lung and lymph node metastasis in CSCC without affecting tumor growth. Pull-down assays revealed that FimA interacts with CD151 and Integrin β1 (ITGB1), which are highly expressed in CSCC cells. Knockdown of CD151 and ITGB1 significantly reduced P. gingivalis adhesion to CSCC cells (P < 0.01) and suppressed its effects on cell migration and invasion (P< 0.05). P. gingivalis treatment activated the JNK/paxillin pathway and triggered actin Cytoskeleton reorganization.

Conclusion: This study identifies P. gingivalis as a tumor-associated bacterium that promotes CSCC metastasis through direct interaction between its fimbrial adhesin FimA and the host CD151/ITGB1 complex. This interaction activates JNK/paxillin signaling, induces cytoskeletal reorganization, and enhances the metastatic capacity of CSCC cells. Targeting this microbial-host interaction may provide a novel therapeutic intervention for P. gingivalis-driven CSCC metastasis.

Keywords

Porphyromonas gingivalis; CD151; Cervical squamous cell carcinoma; ITGB1; Metastasis.

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