TY - JOUR AB - Matriptases, members of the type II transmembrane serine protease family, are cell surface proteolytic enzymes that mediate tumor invasion and metastasis. Matriptase is highly expressed in breast cancer and is associated with poor patient outcome. However, the cellular mechanism by which matriptase mediates breast cancer invasion remains unknown. The present study aimed to determine the role of matriptase in the protein kinase C (PKC)‑mediated metastasis of MCF‑7 human breast cancer cells. Matriptase small interfering RNA‑mediated knockdown significantly attenuated the 12‑O‑tetradecanoylphorbol‑13‑acetate (TPA)‑induced invasiveness and migration of MCF‑7 cells, and inhibited the activation of phospholipase C γ2 (PLCγ2)/PKC/MAPK signaling pathways. Matriptase‑knockdown also suppressed the expression of MMP‑9 and inhibited the activation of NF‑κB/activator protein‑1 in MCF‑7 cells. Additionally, GB83 [an inhibitor of protease‑activated receptor‑2 (PAR‑2)] inhibited PKC‑mediated MMP‑9 expression and metastatic ability in MCF‑7 cells. Furthermore, downregulation of matriptase suppressed TPA‑induced MMP‑9 expression and invasiveness via PAR‑2/PLCγ2/PKC/MAPK activation. These findings shed light on the mechanism underlying the role of matriptase in MCF‑7 cell invasion and migration ability, and suggest that matriptase modulation could be a promising therapeutic strategy for preventing breast cancer metastasis. AD - Department of Biochemistry, Jeonbuk National University Medical School, Jeonju, Jeollabuk 54896, Republic of Korea Department of Internal Medicine, Division of Hematology, Gil Medical Center, Gachon University College of Medicine, Incheon 405‑760, Republic of Korea Department of Oral Biochemistry, School of Dentistry, Wonkwang University, Iksan, Jeollabuk 570‑749, Republic of Korea Department of Surgery, Research Institute of Clinical Medicine, Jeonbuk National University Hospital, Jeonbuk National University and Biomedical Research Institute, Jeonju, Jeollabuk 560‑182, Republic of Korea AU - Kim,Jeong-Mi AU - Park,Jinny AU - Noh,Eun-Mi AU - Song,Hyun-Kyung AU - Kang,Sang,Yull AU - Jung,Sung,Hoo AU - Kim,Jong-Suk AU - Youn,Hyun,Jo AU - Lee,Young-Rae DA - 2021/12/01 DO - 10.3892/or.2021.8198 IS - 6 JO - Oncol Rep KW - matriptase protease‑activated receptor‑2 protein kinase C MMP‑9 invasion breast cancer PY - 2021 SN - 1021-335X 1791-2431 SP - 247 ST - Downregulation of matriptase suppresses the PAR‑2/PLCγ2/PKC‑mediated invasion and migration abilities of MCF‑7 breast cancer cells T2 - Oncology Reports TI - Downregulation of matriptase suppresses the PAR‑2/PLCγ2/PKC‑mediated invasion and migration abilities of MCF‑7 breast cancer cells UR - https://doi.org/10.3892/or.2021.8198 VL - 46 ER -