Skip to main content
Article
Src activates Abl to augment Robo1 expression in order to promote tumor cell migration
Oncotarget (2010)
  • P. Raaj Khusial, Rowan University School of Osteopathic Medicine
  • Bhaskar Vadla, Rowan University School of Osteopathic Medicine
  • Harini Krishnan, Rowan University School of Osteopathic Medicine
  • Trudy F. Ramlall, Weill Medical College of Cornell University
  • Yongquan Shen, Rowan University School of Osteopathic Medicine
  • Hitoshi Ichikawa, National Cancer Center Research Institute (Japan)
  • Jian Guo Geng, University of Minnesota Medical School
  • Gary S. Goldberg, Rowan University School of Osteopathic Medicine
Abstract
Cell migration is an essential step in cancer invasion and metastasis. A number of orchestrated cellular events involving tyrosine kinases and signaling receptors enable cancer cells to dislodge from primary tumors and colonize elsewhere in the body. For example, activation of the Src and Abl kinases can mediate events that promote tumor cell migration. Also, activation of the Robo1 receptor can induce tumor cell migration. However, while the importance of Src, Abl, and Robo1 in cell migration have been demonstrated, molecular mechanisms by which they collectively influence cell migration have not been clearly elucidated. In addition, little is known about
mechanisms that control Robo1 expression. We report here that Src activates Abl to stabilize Robo1 in order to promote cell migration. Inhibition of Abl kinase activity by siRNA or kinase blockers decreased Robo1 protein levels and suppressed the migration of transformed cells. We also provide evidence that Robo1 utilizes Cdc42
and Rac1 GTPases to induce cell migration. In addition, inhibition of Robo1 signaling can suppress transformed cell migration in the face of robust Src and Abl kinase activity. Therefore, inhibitors of Src, Abl, Robo1 and small GTPases may target a coordinated pathway required for tumor cell migration.
Keywords
  • Tyrosine kinase,
  • Src kinase Abl kinase,
  • Robo1,
  • Rho GTPase,
  • Cancer,
  • Cell migration,
  • Cell communication,
  • Connexin
Disciplines
Publication Date
July 20, 2010
DOI
10.18632/oncotarget.126
Publisher Statement
This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Citation Information
P. Raaj Khusial, Bhaskar Vadla, Harini Krishnan, Trudy F. Ramlall, et al.. "Src activates Abl to augment Robo1 expression in order to promote tumor cell migration" Oncotarget Vol. 1 Iss. 3 (2010) p. 198 - 209 ISSN: 1949-2553
Available at: http://works.bepress.com/gary-s-goldberg/8/
Creative Commons license
Creative Commons License
This work is licensed under a Creative Commons CC_BY International License.