a role for pp1nipp1 in steering migration of human cancer cellspp1nipp1的角色转向人类癌细胞的迁移.pdfVIP

A Role for PP1/NIPP1 in Steering Migration of Human Cancer Cells 1 2 3 3 2 Cristina Martin-Granados *, Alan R. Prescott , Nele Van Dessel , Aleyde Van Eynde , Miguel Arocena , 1 ¨ 3 3 3 1 Izabela P. Klaska , Janina Gornemann , Monique Beullens , Mathieu Bollen , John V. Forrester , Colin D. McCaig1* 1 From the Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, United Kingdom, 2 College of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom, 3 Laboratory of Biosignaling Therapeutics, Department of Cellular and Molecular Medicine, University of Leuven, Leuven, Belgium Abstract Electrical gradients are present in many developing and regenerating tissues and around tumours. Mimicking endogenous electric fields in vitro has profound effects on the behaviour of many cell types. Intriguingly, specific cell types migrate cathodally, others anodally and some polarise with their long axis perpendicular to the electric vector. These striking phenomena are likely to have in vivo relevance since one of the determining factors during cancer metastasis is the ability to switch between attractive and repulsive migration in response to extracellular guidance stimuli. We present evidence that the cervical cancer cell line HeLa migrates cathodally in a direct current electric field of physiological intensity, while the strongly metastatic prostate cancer cell line PC-3-M migrates anodally. Notably, genetic disruption of protein serine/ threonine phosphatase-1 (PP1) and its regulator NIPP1 decrease directional migration in these cell lines.