PF-3758309, p21-activated kinase 4 inhibitor, suppresses migration and invasion of A549 human lung cancer cells via regulation of CREB, NF-κB, and β-catenin signalings

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• 作者：Byung Jun Ryu (2)
  Hyuk Lee (3)
  Seong-Ho Kim (3)
  Jung-Nyoung Heo (3)
  Sik-Won Choi (2)
  Jeong-Tae Yeon (4)
  Jeongmin Lee (5)
  Jongsung Lee (6)
  Jae Youl Cho (7)
  Seong Hwan Kim (2)
  Sang Yeol Lee (1)
  
• 关键词：p21 ; activated kinase 4 ; PF ; 3758309 ; CREB ; NF ; κB ; β ; Catenin ; Metastasis ; Matrix metalloproteinases ; Human lung cancer
• 刊名：Molecular and Cellular Biochemistry
• 出版年：2014
• 出版时间：April 2014
• 年：2014
• 卷：389
• 期：1-2
• 页码：69-77
• 全文大小：1,042 KB
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• 作者单位：Byung Jun Ryu (2)
  Hyuk Lee (3)
  Seong-Ho Kim (3)
  Jung-Nyoung Heo (3)
  Sik-Won Choi (2)
  Jeong-Tae Yeon (4)
  Jeongmin Lee (5)
  Jongsung Lee (6)
  Jae Youl Cho (7)
  Seong Hwan Kim (2)
  Sang Yeol Lee (1)
  
  2. Laboratory of Translational Therapeutics, Korea Research Institute of Chemical Technology, Yuseong-Gu, Taejon, 305-600, Korea
  3. Medicinal Chemistry Research Center, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-Gu, Taejon, 305-600, Republic of Korea
  4. Research Institute of Basic Sciences, Sunchon National University, Suncheon, 540-742, Korea
  5. Division of Zoonoses, Korea Center for Disease Control & Prevention, Cheongwon County, Chungcheongbuk-Do, 363-951, Korea
  6. Department of Dermatological Health Management, College of Health Science, Eulji University, Seongnam-Si, Gyeonggi-Do, 461-713, Korea
  7. Department of Genetic Engineering, Sungkyunkwan University, Suwon-Si, Gyeonggi-Do, 440-746, Korea
  1. Department of Life Science, Gachon University, San 65, Bokjeong-Dong, Sujeong-Gu, Seongnam-Si, Gyeonggi-Do, 461-701, Korea
  
• ISSN：1573-4919

文摘

Migration and invasion comprise key steps in cancer metastasis. Through the migration and invasion into and out of lymphatic and/or blood vessels, cancer cells can be spread out into the tissues in remote site from the origin. Degradation of extracellular matrix (ECM) must be preceded prior to the metastasis of cancer cells. Matrix metalloproteinases (MMP) can degrade ECM, thus allow cells to migrate from the original site. Among MMPs, two gelatinase MMP-2 and MMP-9 play particularly important roles in ECM degradation. Here, we report that recently developed p21-activated kinase 4 inhibitor PF-3758309 shows anti-metastatic effect in A549 human lung cancer cell. PF-3758309 suppresses CREB, NF-κB, and β-catenin pathways, which are well known to be closely related with cell migration. This leads to the downregulation of MMP-2/MMP-9 expressions and the inhibition of A549 lung cancer metastasis.