Essential Role of Src Suppressed C Kinase Substrates in Schwann Cells Adhesion, Spreading and Migration

2008 ◽  
Vol 34 (5) ◽  
pp. 1002-1010 ◽  
Author(s):  
Meijuan Yan ◽  
Chun Cheng ◽  
Jing Jiang ◽  
Yonghua Liu ◽  
Ying Gao ◽  
...  
Oncotarget ◽  
2016 ◽  
Vol 7 (39) ◽  
pp. 63816-63828 ◽  
Author(s):  
Jiexia Wen ◽  
Yan Pang ◽  
Tao Zhou ◽  
Ximing Qi ◽  
Min Zhao ◽  
...  

2021 ◽  
Author(s):  
Annalena Wieland ◽  
Pamela L. Strissel ◽  
Hannah Schorle ◽  
Ezgi Bakirci ◽  
Dieter Janzen ◽  
...  

Abstract Background: Glioblastoma multiforme (GBM) and triple-negative breast cancer (TNBC) with PTEN mutations often lead to brain dissemination with very poor patient outcomes. GBM uses axons and vessels as migratory cues to disseminate, however it is not known, if TNBC shares the same behavior. There is a need to understand brain tumor cell spreading and if GBM and TNBC have similar migration properties involving the signaling pathway RHOB-ROCK-PTEN. We tested for durotaxis, adherence and migration of GBM and TNBC using live-cell imaging and performed molecular analyses on three-dimensional (3D) structures.Methods: Aligned 3D printed scaffolds and microfibers were designed to mimic brain axon tracts and vessels for migration. GBM and TNBC cell lines, each with opposing PTEN genotypes, were analysed with RHO, ROCK and PTEN inhibitors and rescuing PTEN function using live-cell imaging. RNA-sequencing and qPCR of tumor cells in 3D with microfibers were performed, while SEM, confocal microscopy and cell tracking addressed cell morphology. Results: GBM and TNBC with homozygote PTEN loss of function and RHOB high expression were amoeboid shaped and demonstrated enhanced durotaxis, adhesion and migration on 3D microfibers, in contrast to PTEN wildtype GBM and TNBC showing elongated cells and low RHOB. RNA-sequencing exhibited that RHOB was significantly the highest expressed gene in GBM PTEN loss of function cells. Pathway inhibitors and PTEN rescue of function verified an essential role of RHOB-ROCK-PTEN signaling for durotaxis, adhesion, migration, cell morphology and plasticity using 3D printed microfibers. Conclusions: This study validates a significant role of a PTEN genotype for cellular properties including durotaxis, adhesion and migration. GBM and TNBC cells with PTEN loss of function have a greater affinity for stiffer brain structures promoting metastasis. We propose the significance of PTEN and RHOB in cellular oncology not only for primary tumors, but also for metastasizing tumors, where RHOB inhibitors could play an essential role for improved therapy.


Oncogene ◽  
2012 ◽  
Vol 32 (43) ◽  
pp. 5144-5155 ◽  
Author(s):  
D Kesanakurti ◽  
C Chetty ◽  
D Rajasekhar Maddirela ◽  
M Gujrati ◽  
J S Rao

1982 ◽  
Vol 93 (1) ◽  
pp. 211-216 ◽  
Author(s):  
A Baron-Van Evercooren ◽  
H K Kleinman ◽  
H E Seppä ◽  
B Rentier ◽  
M Dubois-Dalcq

Techniques are now available for culturing well characterized and purified Schwann cells. Therefore, we investigated the role of fibronectin in the adhesion, growth, and migration of cultured rat Schwann cells. Double-immunolabeling shows that, in primary cultures of rat sciatic nerve, Schwann cells (90%) rarely express fibronectin, whereas fibroblasts (10%) exhibit a granular cytoplasmic and fibrillar surface-associated fibronectin. Secondary cultures of purified Schwann cells do not express fibronectin. Exogenous fibronectin has a small effect on promoting the adhesion of Schwann cells to the substrate and does not significantly affect cell morphology, but it produced a surface fibrillar network on fibronectin on the secondary Schwann cells. Tritiated thymidine autoradiography revealed that addition of fibronectin to the medium, even at low concentrations, markedly stimulates Schwann cell proliferation, in both primary and secondary cultures. In addition, when cell migration was measured in a Boyden chamber assay, fibronectin was found to moderately, but clearly, stimulate directed migration or chemotaxis.


2007 ◽  
Vol 358 (1) ◽  
pp. 342-348 ◽  
Author(s):  
Chun Cheng ◽  
Haiou Liu ◽  
Haiyan Ge ◽  
Ji Qian ◽  
Jing Qin ◽  
...  

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