Synthetic D-amino acid peptide inhibits tumor cell motility on laminin-5

Thomas C. Sroka, Michael E. Pennington, Anne E Cress

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Cell motility is partially dependent on interactions between the integrins and the extracellular matrix. Our previous studies have identified synthetic D-amino acid cell adhesion peptides using a combinatorial screening approach. In this study, we demonstrate that HYD1 (kikmviswkg) completely blocks random haptotactic migration and inhibits invasion of prostate carcinoma cells on laminin-5. This effect is adhesion independent and reversible. The inhibition of migration by HYD1 involves a dramatic remodeling of the actin cytoskeleton resulting in increased stress fiber formation and actin colocalization with cortactin at the cell membrane. HYD1 interacts with α6β1 (not α6β4) and α3β1 integrins and surprisingly elevates laminin-5-dependent intracellular signals including focal adhesion kinase, mitogen-activated protein kinase kinase and extracellular signal-regulated kinase. HYD1 does not contain a previously characterized binding sequence for integrins. A scrambled derivative of HYD1, called HYDS (wiksmkivkg), does not interact with the α6 or α3 integrin subunits and is not biologically active. Taken together, these results indicate that HYD1 is a biologically active integrin-targeting peptide that reversibly inhibits tumor cell migration on laminin-5 and uncouples phosphotyrosine signaling from cytoskeletal-dependent migration.

Original languageEnglish (US)
Pages (from-to)1748-1757
Number of pages10
JournalCarcinogenesis
Volume27
Issue number9
DOIs
StatePublished - Sep 2006

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Integrins
Cell Movement
Amino Acids
Peptides
Neoplasms
Cortactin
MAP Kinase Kinase Kinases
Focal Adhesion Protein-Tyrosine Kinases
Stress Fibers
Phosphotyrosine
Extracellular Signal-Regulated MAP Kinases
Actin Cytoskeleton
Cell Adhesion
Extracellular Matrix
Actins
Prostate
Cell Membrane
kalinin
Carcinoma

ASJC Scopus subject areas

  • Cancer Research

Cite this

Synthetic D-amino acid peptide inhibits tumor cell motility on laminin-5. / Sroka, Thomas C.; Pennington, Michael E.; Cress, Anne E.

In: Carcinogenesis, Vol. 27, No. 9, 09.2006, p. 1748-1757.

Research output: Contribution to journalArticle

Sroka, Thomas C. ; Pennington, Michael E. ; Cress, Anne E. / Synthetic D-amino acid peptide inhibits tumor cell motility on laminin-5. In: Carcinogenesis. 2006 ; Vol. 27, No. 9. pp. 1748-1757.
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