Src Activates Abl to Augment Robo1 Expression in Order to Promote Tumor Cell Migration

Overview

Journal Oncotarget

Specialty Oncology

Date 2011 Feb 9

PMID 21301049

Citations 15

Authors

P Raaj Khusial

Bhaskar Vadla

Harini Krishnan

Trudy F Ramlall

Yongquan Shen

Hitoshi Ichikawa

Jian-Guo Geng

Gary S Goldberg

Affiliations

Soon will be listed here.

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.

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