BACKGROUND: Invasion and metastatic dissemination of tumor cells defines the prognosis of patients with colorectal cancer (CRC). The Abelson interactor 1 (Abi1), a 65 kD substrate of the eponymous Abelson tyrosine kinase, interacts with phosphatidylinositol-3-kinase (PI3K) and heterogeneous nuclear ribonucleoprotein K (hnRNP K) and is a key regulator of cytoskeletal reorganization during synaptic maturation and cellular migration. AIM: The aim of this study was the analysis of Abi1 expression patterns and to elucidate the role in cytoskeletal reorganization in colorectal carcinoma cells. MATERIAL AND METHODS: The methods used in this study were immunohistochemistry; immunofluorescence microscopy; liposomal transfection and protein analysis by Western blotting. RESULTS: The results showed that Abi1 is expressed at the invasive front of colorectal carcinomas and localizes to the leading edge of lamellipodia in cultured colorectal carcinoma cells. A phosphorylated isoform of Abi1 that stains positively in these microcompartments disappears after treatment with the tyrosine kinase inhibitor STI571 (Glivec®). The RNA interference (RNAi) approach knockdown of Abi1 as well as treatment with STI571 induce a shift in cellular morphology from broad lamellipodia-like to thin filopodia-like cellular protrusions. DISCUSSION: The initial results support a central role for phosphorylated Abi1 in the formation of lamellipodia-like cellular protrusions as a prerequisite for cellular migration of colorectal carcinoma cells. As phosphorylation of Abi1 could be pharmaceutically targeted with STI571, this indicates a possible therapeutic option to prevent the gain of a metastatic phenotype in colorectal cancer. This possibility will be further evaluated in ongoing research.
BACKGROUND: Invasion and metastatic dissemination of tumor cells defines the prognosis of patients with colorectal cancer (CRC). The Abelson interactor 1 (Abi1), a 65 kD substrate of the eponymous Abelson tyrosine kinase, interacts with phosphatidylinositol-3-kinase (PI3K) and heterogeneous nuclear ribonucleoprotein K (hnRNP K) and is a key regulator of cytoskeletal reorganization during synaptic maturation and cellular migration. AIM: The aim of this study was the analysis of Abi1 expression patterns and to elucidate the role in cytoskeletal reorganization in colorectal carcinoma cells. MATERIAL AND METHODS: The methods used in this study were immunohistochemistry; immunofluorescence microscopy; liposomal transfection and protein analysis by Western blotting. RESULTS: The results showed that Abi1 is expressed at the invasive front of colorectal carcinomas and localizes to the leading edge of lamellipodia in cultured colorectal carcinoma cells. A phosphorylated isoform of Abi1 that stains positively in these microcompartments disappears after treatment with the tyrosine kinase inhibitor STI571 (Glivec®). The RNA interference (RNAi) approach knockdown of Abi1 as well as treatment with STI571 induce a shift in cellular morphology from broad lamellipodia-like to thin filopodia-like cellular protrusions. DISCUSSION: The initial results support a central role for phosphorylated Abi1 in the formation of lamellipodia-like cellular protrusions as a prerequisite for cellular migration of colorectal carcinoma cells. As phosphorylation of Abi1 could be pharmaceutically targeted with STI571, this indicates a possible therapeutic option to prevent the gain of a metastatic phenotype in colorectal cancer. This possibility will be further evaluated in ongoing research.
Authors: Marisan R Mejillano; Shin-ichiro Kojima; Derek Anthony Applewhite; Frank B Gertler; Tatyana M Svitkina; Gary G Borisy Journal: Cell Date: 2004-08-06 Impact factor: 41.582
Authors: Christian Proepper; Svenja Johannsen; Stefan Liebau; Janine Dahl; Bianca Vaida; Juergen Bockmann; Michael R Kreutz; Eckart D Gundelfinger; Tobias M Boeckers Journal: EMBO J Date: 2007-02-15 Impact factor: 11.598
Authors: Stefan Liebau; Julie Steinestel; Leonhard Linta; Alexander Kleger; Alexander Storch; Michael Schoen; Konrad Steinestel; Christian Proepper; Juergen Bockmann; Michael J Schmeisser; Tobias M Boeckers Journal: PLoS One Date: 2011-03-25 Impact factor: 3.240
Authors: Christian Proepper; Konrad Steinestel; Michael J Schmeisser; Jutta Heinrich; Julie Steinestel; Juergen Bockmann; Stefan Liebau; Tobias M Boeckers Journal: PLoS One Date: 2011-11-15 Impact factor: 3.240
Authors: Konrad Steinestel; Silke Brüderlein; Julie Steinestel; Bruno Märkl; Michael J Schwerer; Annette Arndt; Klaus Kraft; Christian Pröpper; Peter Möller Journal: PLoS One Date: 2012-07-10 Impact factor: 3.240