Abstract 483: Serine phosphorylation of vasodilator-stimulated phosphoprotein defines the malignant cell phenotype in colon cancer

Abstract

Abstract Metastasis is the principal pathological process underlying mortality for colorectal cancer, the third deadly cancer worldwide. During tumor invasion, cancer cells assume a mesenchymal morphology that confers migratory and proliferative advantages. One of the mechanisms regulating malignant cell shape is the activity of the vasodilator-stimulated phosphoprotein (VASP) on the actin cytoskeleton. Here, human colon carcinoma cells were treated with cell permeant analogs of cAMP or cGMP, to preferentially induce VASP Ser157 (pVASP-Ser157) or Ser239 (pVASP-Ser239) phosphorylation, and examined by confocal microscopy, western blotting and colony formation. Confirming previous results, cancer dynamic membrane regions formed by the actin cytoskeleton were differentially modulated by VASP Ser phosphorylation. However, treatments with cAMP, which promoted a mesenchymal cell phenotype, reduced E-cadherin at tumor cell-cell junctions and enhanced vimentin and vinculin levels. In contrast cGMP induced an opposite cell morphology with increased E-cadherin-rich cell-cell contacts and decreased cellular vimentin and vinculin. Moreover, the cAMP-dependent phenotype increased the cancer cell ability to form tumor colonies, while cGMP compromised that metastatic potential. Importantly, cyclic nucleotide effects were mediated by selective VASP Ser phosphorylation, because VASP phosphomutants at Ser157 and Ser239 blocked cAMP or cGMP actions, respectively. Together, these findings suggest that in colon cancer cells pVASP-Ser157 and pVASP-Ser239 are critical determinants of the malignant phenotype, which define the function of actin cytoskeletal regulators, invasive cell morphology and tumorigenic potential. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 483. doi:1538-7445.AM2012-483