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Writing Assignment Introduction and Hypothesis

Fibronectin is one of the key proteins produced by humans to glue our bodies together and several other functions. Figure A shows a PYMOL rendering of the quaternary structure of the FN1 protein. Fibronectin is secreted by a multitude of cell types and bound together by disulfide bonds with 230-270 kDa subunits. (Mao) FN1 serves our body primarily through creating substances for adhesion, but it also contributes to cytoskeleton formation, cell migration, and wound healing. (Goossens 2009) It can enact this multitude of purposes through various isoforms created as a result of alternative splicing.

The expression level and amount of each isoform changes throughout one’s life with various levels during embryotic development and when one is injured or ill. (Goossens 2009) Fibronectin is also shown to have negative interactions within the body. Some isoforms not only stimulate lung Carcinoma; it also makes it more resilient to apoptosis. (Han)

One hypothesis from this information could be: if the expression of the harmful isoform of fibronectin was inhibited in a lung carcinoma, then a decrease or halting of the carcinoma size would be observable. There are several ways this could be approached. A virally delivered CRISPR-cas9 construct that replaces the destructive isoform gene with a cancer inhibiting version would likely be the easiest. A more difficult route would be to create a drug that contains a protein that has incredibly high affinity for the destructive isoform. This would stick to bind to the fibronectin and cause steric hindrance.

Figure A.

Literature Cited

Goossens K, Van Soom A, Zeveren A, Favoreel H, Peelman L. 2009. Quantification of fibronectin 1 (FN1) splice variants, including two novel ones, and analysis of integrins as candidate FN1 receptors in bovine preimplantation embryos. BMC. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2648952/ DOI: 10.1186/1471-213X-9-1

Han S, Khuri F, Roman J. 2006. Fibronectin stimulates non–small cell lung carcinoma cell growth through activation of akt/mammalian target of rapamycin/S6 kinase and inactivation of lKB1/AMP activated protein kinase signal pathways. Cancer Res. Available from: https://cancerres.aacrjournals.org/content/66/1/315 DOI: 10.1158/0008-5472.

Mao Y, Schwarzbauer J. 2005. Fibronecting fibrillogenesis, a cell mediated matrix assembly process. Matrix Biol. 24:389-399. Available from: https://www.sciencedirect.com/science/article/pii/S0945053X05000855