A holistic approach to dissecting SPARC family protein complexity reveals FSTL-1 as an inhibitor of pancreatic cancer cell growth
| Autor: | Sharan Asher, Natasha J. Hill, Roberto Bogyere, Katrina Viloria, Lucy Jones, Amanda Munasinghe |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Signal peptide Stromal cell Follistatin-Related Proteins Down-Regulation Biology Bioinformatics Article 03 medical and health sciences Islets of Langerhans Mice 0302 clinical medicine Calcium-binding protein Pancreatic cancer Cell Line Tumor medicine Animals Humans Cell Proliferation Regulation of gene expression Extracellular Matrix Proteins Multidisciplinary Alternative splicing Matricellular protein Calcium-Binding Proteins medicine.disease Cell biology Gene Expression Regulation Neoplastic Pancreatic Neoplasms Alternative Splicing 030104 developmental biology 030220 oncology & carcinogenesis Proteoglycans Protein Processing Post-Translational Neoplasm Transplantation biological |
| Zdroj: | Scientific Reports |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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