Large-scale identification of functional genes regulating cancer cell migration and metastasis using the self-assembled cell microarray
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Metastasis is one of the critical hallmarks of malignancy tumor and the principal cause of death in patients with cancer. Cell migration is the basic and essential step in cancer metastasis process. To systematically investigate functional genes regulating cell migration and cancer metastasis on large scale, we developed a novel on-chip method, SAMcell (self-assembled cell microarray). This method was demonstrated to be particularly suitable for loss-of-function high-throughput screening because of its unique advantages. The first application of SAMcell was to screen human genome miRNAs, considering that more and more miRNAs had been proved to govern cancer metastasis. We found that over 20 % of miRNAs have migratory regulation activity in diverse cell types, indicating a general involvement of miRNAs in migratory regulation. Through triple-round screenings, we discovered miR-23b, which is down-regulated in human colon cancer samples, potently mediates the multiple steps of metastasis, including cell motility, cell growth and cell survival. In parallel, the second application of SAMcell was to screen human genome kinase genes, considering that more and more kinase genes had become successful diagnostic marker or drug targets. We found over 11% migratory kinase genes, suggesting the important role of kinase group in metastasis regulation. Through both functional screening and bioinformatics analysis, we discovered and validated 6 prospective metastasis-related kinase genes, which can be new potential targets in cancer therapy. These findings allow the understanding of regulation mechanism in human cancer progression, especially metastasis and provide the new insight into the biological and therapeutical importance of miRNAs or kinases in cancer.