The Rho guanine nucleotide exchange factor Syx regulates the balance of dia and ROCK activities to promote polarized-cancer-cell migration

Justus C. Dachsel, Siu P. Ngok, Laura J. Lewis-Tuffin, Antonis Kourtidis, Rory Geyer, Lauren Johnston, Ryan Feathers, Panagiotis Z Anastasiadis

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The role of RhoA in promoting directed cell migration has been complicated by studies showing that it is activated both in the front and the rear of migrating cells. We report here that the RhoA-specific guanine nucleotide exchange factor Syx is required for the polarity of actively migrating brain and breast tumor cells. This function of Syx is mediated by the selective activation of the RhoA downstream effector Dia1, the subsequent reorganization of microtubules, and the downregulation of focal adhesions and actin stress fibers. The data argue that directed cell migration requires the precise spatiotemporal regulation of Dia1 and ROCK activities in the cell. The recruitment of Syx to the cell membrane and the subsequent selective activation of Dia1 signaling, coupled with the suppression of ROCK and activation of cofilin-mediated actin reorganization, plays a key role in establishing cell polarity during directed cell migration.

Original languageEnglish (US)
Pages (from-to)4909-4918
Number of pages10
JournalMolecular and Cellular Biology
Volume33
Issue number24
DOIs
StatePublished - 2013

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Rho Guanine Nucleotide Exchange Factors
Cell Movement
Actins
Actin Depolymerizing Factors
Guanine Nucleotide Exchange Factors
Neoplasms
Stress Fibers
Cell Polarity
Focal Adhesions
Brain Neoplasms
Microtubules
Down-Regulation
Cell Membrane
Breast Neoplasms

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

The Rho guanine nucleotide exchange factor Syx regulates the balance of dia and ROCK activities to promote polarized-cancer-cell migration. / Dachsel, Justus C.; Ngok, Siu P.; Lewis-Tuffin, Laura J.; Kourtidis, Antonis; Geyer, Rory; Johnston, Lauren; Feathers, Ryan; Anastasiadis, Panagiotis Z.

In: Molecular and Cellular Biology, Vol. 33, No. 24, 2013, p. 4909-4918.

Research output: Contribution to journalArticle

Dachsel, Justus C. ; Ngok, Siu P. ; Lewis-Tuffin, Laura J. ; Kourtidis, Antonis ; Geyer, Rory ; Johnston, Lauren ; Feathers, Ryan ; Anastasiadis, Panagiotis Z. / The Rho guanine nucleotide exchange factor Syx regulates the balance of dia and ROCK activities to promote polarized-cancer-cell migration. In: Molecular and Cellular Biology. 2013 ; Vol. 33, No. 24. pp. 4909-4918.
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