Caleb Sooknanan ‘20

Cancer metastasis refers to the spread of cancer cells from an original tumor to another bodily region through a subject’s blood or lymph systems. The possibility of cancer cells entering a subject’s blood stream is mainly dependent upon the motility of cancer cells within the subject’s body. However, more research is needed to understand and detect the genes that account for cancer cell motility within tumor environments. Doctor John D. Lewis and researchers from the University of Alberta in Canada developed a quantitative screening platform that would utilize images of human cancer metastasis in shell-less avian embryos to detect genes needed for cancer cell motility. The researchers would use this new platform to screen a series of genomes and determine genes that would be more closely associated with metastatic risks among human cancers. These tasks were performed to understand whether the targeting of these genes could inhibit cancer cell progression throughout a patient’s body.

To conduct this study, the researchers utilized a molecular system known as a knockout library to insert short hairpin RNA or shRNA vectors into a series of cancer cells. The shRNA vectors, or artificial RNA molecules normally used to silent target gene expression using RNA interference, were bound to specific genes within the cells to prevent activation. The researchers inserted the resulting cells into avian embryos and observed the formation of cancerous cell clusters. When they found such cell clusters, the researchers recognized that all genetic steps associated with cell metastasis were being blocked for those clusters, allowing them to query distinct gene sequences and validate whether the genes were directly responsible for cell metastasis. The researchers further verified their gene identification by performing high-resolution, time-lapse imaging of the metastatic cell colonies.

According to the screening results, 11 genes were detected and identified as being directly associated with cancer cell metastasis. The researchers stated that these genes had previously been known to influence cancer cell migration and invasion within a given subject. However, the researchers noted that the gene KIF3B — one of the 11 genes found to be linked to cancer metastasis — was also associated with cellular transportation, so more work is needed to understand this function. Nevertheless, the researchers plan to test the detected genes as drug targets and thereby provide more effective treatments for metastasis.

References

1. J. Lewis, et. al., Quantitative in vivo whole genome motility screen reveals novel therapeutic targets to block cancer metastasis. Nature Communications 9 (2018). doi: 10.1038/s41467-018-04743-2.  
2. Image retrieved from: https://www.maxpixel.net/static/photo/1x/Dna-Molecule-Medicine-1903875.jpg