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Microfluidic Cell Deformability Assay for Rapid and Efficient Kinase Screening with the CRISPR-Cas9 System
Microfluidic Cell Deformability Assay for Rapid and Efficient Kinase Screening with the CRISPR-Cas9 System
- Source :
- Angewandte Chemie (International Ed. in English)
- Publication Year :
- 2016
- Publisher :
- Wiley, 2016.
-
Abstract
- Herein we report a CRISPR‐Cas9‐mediated loss‐of‐function kinase screen for cancer cell deformability and invasive potential in a high‐throughput microfluidic chip. In this microfluidic cell separation platform, flexible cells with high deformability and metastatic propensity flowed out, while stiff cells remained trapped. Through deep sequencing, we found that loss of certain kinases resulted in cells becoming more deformable and invasive. High‐ranking candidates identified included well‐reported tumor suppressor kinases, such as chk2, IKK‐α, p38 MAPKs, and DAPK2. A high‐ranking candidate STK4 was chosen for functional validation and identified to play an important role in the regulation of cell deformability and tumor suppression. Collectively, we have demonstrated that CRISPR‐based on‐chip mechanical screening is a potentially powerful strategy to facilitate systematic genetic analyses.
- Subjects :
- 0301 basic medicine
Cytochalasin D
p38 mitogen-activated protein kinases
Microfluidics
Cell
Protein Serine-Threonine Kinases
Analytical Methods
p38 Mitogen-Activated Protein Kinases
Catalysis
Deep sequencing
03 medical and health sciences
0302 clinical medicine
cell deformability
Cell Movement
Cell Line, Tumor
Lab-On-A-Chip Devices
medicine
Humans
CRISPR
Dimethyl Sulfoxide
Checkpoint Kinase 2
Chemistry
Kinase
Communication
Intracellular Signaling Peptides and Proteins
I-Kappa-B Kinase
biomarkers
General Chemistry
General Medicine
Molecular biology
Communications
I-kappa B Kinase
Cell biology
Death-Associated Protein Kinases
medicine.anatomical_structure
030104 developmental biology
Microscopy, Fluorescence
030220 oncology & carcinogenesis
Cancer cell
CRISPR-Cas9
CRISPR-Cas Systems
Protein Kinases
Subjects
Details
- ISSN :
- 00448249
- Volume :
- 128
- Database :
- OpenAIRE
- Journal :
- Angewandte Chemie
- Accession number :
- edsair.doi.dedup.....459d017ae71d4a2bc4ac3ce8d3fb01ad
- Full Text :
- https://doi.org/10.1002/ange.201601984