Expression and Y435-phosphorylation of Abelson interactor 1 (Abi1) promotes tumour cell adhesion, extracellular matrix degradation and invasion by colorectal carcinoma cells

Molecular Cancer

Research

Viktor Meineke¹  Konrad Steinestel²  Julie Steinestel³  Christian Pröpper⁴  Klaus Kraft⁵  Peter Möller⁶  Silke Brüderlein⁶  Jochen K Lennerz⁶ 

[1] Bundeswehr Institute of Radiobiology, Neuherbergstr. 11, 80937, Munich, Germany;Bundeswehr Institute of Radiobiology, Neuherbergstr. 11, 80937, Munich, Germany;Institute of Pathology, University Hospital, Ulm, Germany;Clinic of Urology, University Hospital, Ulm, Germany;Institute of Anatomy and Cell Biology, University of Ulm, Ulm, Germany;Institute of Pathology and Molecular Pathology, Bundeswehrkrankenhaus, Ulm, Germany;Institute of Pathology, University Hospital, Ulm, Germany;

关键词: Abelson interactor 1 (Abi1);    Colorectal carcinoma;    Extracellular matrix (ECM);    Invasion;    Metastasis;   

DOI  :  10.1186/1476-4598-13-145

 received in 2014-02-04, accepted in 2014-06-02,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundThe Abelson tyrosine kinase (c-Abl) inhibitor STI571 (Glivec®) has been shown to effectively inhibit colorectal cancer cell migration and invasion. The c-Abl substrate abelson interactor 1 (Abi1) is a key regulator of actin reorganization and upregulated in colorectal carcinoma. The specific role of Abi1 in relation to extracellular matrix degradation and effects of targeting Abi1 phosphorylation have not yet been examined. Here, we investigated the role of Abi1 in relation to invasive properties in colorectal cancer.Methods and resultsIn 56 primary human colorectal carcinoma samples, we found overexpression of Abi1 in 39% at the invasive edge of the tumour, associated with an infiltrative phenotype and high-grade tumour cell budding (p = 0.001). To explore the role of Abi1 in vitro, we employed the Abi1 expressing and KRAS-mutated CHD1 model and performed matrix degradation assays that showed Abi1 localization at specific sites of matrix degradation. Moreover, quantification of matrix dissolution demonstrated suppression after RNAi knockdown of Abi1 by 95% (p = 0.001). Importantly, treatment with STI571 did abolish Abi1 Y435-phosphorylation, suppressed the matrix dissolution, decreased fibronectin attachment, and suppressed cell invasion through reconstituted extracellular matrix.ConclusionOur data indicate that phosphorylated Abi1 contributes to the invasive properties of colorectal cancer.

【 授权许可】

CC BY   
© Steinestel et al.; licensee BioMed Central Ltd. 2014