A holistic approach to dissecting SPARC family protein complexity reveals FSTL-1 as an inhibitor of pancreatic cancer cell growth

Viloria, Katrina, Munasinghe, Amanda, Asher, Sharan, Bogyere, Roberto, Jones, Lucy and Hill, Natasha (2016) A holistic approach to dissecting SPARC family protein complexity reveals FSTL-1 as an inhibitor of pancreatic cancer cell growth. Scientific Reports, 6, p. 37839. ISSN (online) 2045-2322

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SPARC is a matricellular protein that is involved in both pancreatic cancer and diabetes. It belongs to a wider family of proteins that share structural and functional similarities. Relatively little is known about this extended family, but evidence of regulatory interactions suggests the importance of a holistic approach to their study. We show that Hevin, SPOCKs, and SMOCs are strongly expressed within islets, ducts, and blood vessels, suggesting important roles for these proteins in the normal pancreas, while FSTL-1 expression is localised to the stromal compartment reminiscent of SPARC. In direct contrast to SPARC, however, FSTL-1 expression is reduced in pancreatic cancer. Consistent with this, FSTL-1 inhibited pancreatic cancer cell proliferation. The complexity of SPARC family proteins is further revealed by the detection of multiple cell-type specific isoforms that arise due to a combination of post-translational modification and alternative splicing. Identification of splice variants lacking a signal peptide suggests the existence of novel intracellular isoforms. This study underlines the importance of addressing the complexity of the SPARC family and provides a new framework to explain their controversial and contradictory effects. We also demonstrate for the first time that FSTL-1 suppresses pancreatic cancer cell growth.

Item Type: Article
Additional Information: This work was funded by the IhSHA research hub at Kingston University.
Research Area: Biological sciences
Faculty, School or Research Centre: Faculty of Science, Engineering and Computing (until 2017) > School of Life Sciences
Depositing User: Susan Miles
Date Deposited: 13 Dec 2016 10:19
Last Modified: 30 Jun 2017 10:51
DOI: https://doi.org/10.1038/srep37839
URI: http://eprints.kingston.ac.uk/id/eprint/36358

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