2. Academic Validation
  3. Phenyllactic acid promotes cell migration and invasion in cervical cancer via IKK/NF-κB-mediated MMP-9 activation

Phenyllactic acid promotes cell migration and invasion in cervical cancer via IKK/NF-κB-mediated MMP-9 activation

  • Cancer Cell Int. 2019 Sep 23;19:241. doi: 10.1186/s12935-019-0965-0.
Chao Li  # 1,  Yanfei Li  # 2,  Lanxia Sui 3,  Jian Wang 4,  Fang Li 5
Affiliations

Affiliations

  • 1 1Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, No. 2699, West GaoKe Road, Shanghai, 201204 China.
  • 2 2School of Medical Technology, Shanghai University of Medicine & Health Sciences, Shanghai, 201318 China.
  • 3 Department of Pediatrics, PLA No. 904 Hospital, Wuxi, 214000 China.
  • 4 4School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025 China.
  • 5 5Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, No. 2699, West GaoKe Road, Shanghai, 201204 China.
  • # Contributed equally.
PMID: 31572058 DOI: 10.1186/s12935-019-0965-0
Abstract

Background: Persistent Infection with high-risk human papillomavirus (hrHPV) is associated with cervical Cancer development. This process involves the virus-encoded E6 and E7 oncoproteins, which are maintained and expressed during all malignant transformation stages. However, HPV alone is insufficient to drive tumor progression-related behaviors such as cervical Cancer cell motility. In this study, we investigated the effect of phenyllactic acid (PLA), a phenolic acid phytochemical and biomarker for discriminating various cancers, on the metastatic potential of cervical Cancer cells.

Methods: The effects of PLA on HPV16/18 E6/E7 expression, migratory and invasive behavior, and Matrix Metalloproteinases (MMPs) expression of cervical cancers cells were measured. Specific inhibitors were used to further investigate biological function and underlying mechanism of PLA modulated cell motility.

Results: PLA significantly promoted the migration and invasion of SiHa, HeLa, and C-33A cervical Cancer cells as well as upregulated matrix metalloproteinase-9 (MMP-9) expression. Moreover, PLA treatment attenuated E6/E7 expression in SiHa and HeLa cells. Further molecular analysis showed that PLA activated the nuclear factor-kappa B (NF-κB) signaling pathway and increased the nuclear translocation of both IκBα and p65. Treating cervical Cancer cells with an NF-κB Inhibitor potently reversed PLA-induced migratory and invasive behavior, MMP-9 upregulation, and/or E6/E7 downregulation. The PLA-induced NF-κB activation and MMP-9 upregulation were mediated by IκB kinase-β (IKK-β) phosphorylation via PKC signals. The results suggested that SiHa, HeLa, and C-33A cells might undergo a similar process to enhance their motility in response to PLA, regardless of the HPV status.

Conclusions: Collectively, our study reveals a new biological function of PLA and elucidate the possible molecular role of PLA as a risk factor for triggering cervical Cancer cell motility.

Keywords

Cervical cancer; Human papillomavirus; Migration and invasion; NF-κB; Phenyllactic acid.

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