title: Lysophosphatidic acid induces MDA-MB-231 breast cancer cells migration through activation of PI3K/PAK1/ERK signaling.
abstract: BACKGROUND
  Enhanced motility of cancer cells is a critical step in promoting tumor metastasis. Lysophosphatidic acid (LPA), representing the major mitogenic activity in serum, stimulates migration in various types of cancer cells. However, the underlying signaling mechanisms for LPA-induced motility of cancer cells remain to be elucidated.
  
  
  RESULTS
  In this study, we found that LPA dose-dependently stimulated migration of MDA-MB-231 breast cancer cells, with 10 µM being the most effective. LPA also increased ERK activity and the MEK inhibitor U0126 could block LPA-induced ERK activity and cell migration. In addition, LPA induced PAK1 activation while ERK activation and cell migration were inhibited by ectopic expression of an inactive mutant form of PAK1 in MDA-MB-231 cells. Furthermore, LPA increased PI3K activity, and the PI3K inhibitor LY294002 inhibited both LPA-induced PAK1/ERK activation and cell migration. Moreover, in the breast cancer cell, LPA treatment resulted in remarkable production of reactive oxygen species (ROS), while LPA-induced ROS generation, PI3K/PAK1/ERK activation and cell migration could be inhibited by N-acetyl-L-Cysteine, a scavenger of ROS.
  
  
  CONCLUSIONS
  Taken together, this study identifies a PI3K/PAK1/ERK signaling pathway for LPA-stimulated breast cancer cell migration. These data also suggest that ROS generation plays an essential role in the activation of LPA-stimulated PI3K/PAK1/ERK signaling and breast cancer cell migration. These findings may provide a basis for designing future therapeutic strategy for blocking breast cancer metastasis.
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Du
authors.forename: Chongqi
authors.initials: C
authors.lastname: Sun
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Hu
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.forename: Yichao
authors.initials: Y
authors.lastname: Zhu
authors.forename: Datong
authors.initials: D
authors.lastname: Zheng
authors.forename: Luo
authors.initials: L
authors.lastname: Gu
authors.forename: Xiang
authors.initials: X
authors.lastname: Lu
mesh_terms: D000111:Acetylcysteine / Q000737:chemistry; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism*; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D054462:p21-Activated Kinases / Q000378:metabolism*
chemical_list: D008246:Lysophospholipids; D017382:Reactive Oxygen Species; D019869:Phosphatidylinositol 3-Kinases; C515903:PAK1 protein, human; D054462:p21-Activated Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; C032881:lysophosphatidic acid; D000111:Acetylcysteine