Coupling S100A4 to Rhotekin alters Rho signaling output in breast cancer cells

M. Chen, Anne R. Bresnick, K. L. O'Connor

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Rho signaling is increasingly recognized to contribute to invasion and metastasis. In this study, we discovered that metastasis-associated protein S100A4 interacts with the Rho-binding domain (RBD) of Rhotekin, thus connecting S100A4 to the Rho pathway. Glutathione S-transferase pull-down and immunoprecipitation assays demonstrated that S100A4 specifically and directly binds to Rhotekin RBD, but not the other Rho effector RBDs. S100A4 binding to Rhotekin is calcium-dependent and uses residues distinct from those bound by active Rho. Interestingly, we found that S100A4 and Rhotekin can form a complex with active RhoA. Using RNA interference, we determined that suppression of both S100A4 and Rhotekin leads to loss of Rho-dependent membrane ruffling in response to epidermal growth factor, an increase in contractile F-actin 'stress' fibers and blocks invasive growth in three-dimensional culture. Accordingly, our data suggest that interaction of S100A4 and Rhotekin permits S100A4 to complex with RhoA and switch Rho function from stress fiber formation to membrane ruffling to confer an invasive phenotype.

Original languageEnglish (US)
Pages (from-to)3754-3764
Number of pages11
JournalOncogene
Volume32
Issue number32
DOIs
StatePublished - Aug 8 2013

Fingerprint

Stress Fibers
Breast Neoplasms
Neoplasm Metastasis
Membranes
RNA Interference
Glutathione Transferase
Immunoprecipitation
Epidermal Growth Factor
Actins
Calcium
Phenotype
Growth
S100 Calcium-Binding Protein A4

Keywords

  • invasive growth
  • lamellipodia
  • Rho
  • Rhotekin
  • S100A4/metastasin

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Coupling S100A4 to Rhotekin alters Rho signaling output in breast cancer cells. / Chen, M.; Bresnick, Anne R.; O'Connor, K. L.

In: Oncogene, Vol. 32, No. 32, 08.08.2013, p. 3754-3764.

Research output: Contribution to journalArticle

Chen, M. ; Bresnick, Anne R. ; O'Connor, K. L. / Coupling S100A4 to Rhotekin alters Rho signaling output in breast cancer cells. In: Oncogene. 2013 ; Vol. 32, No. 32. pp. 3754-3764.
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