Pub Date : 2018-01-01Epub Date: 2018-12-16DOI: 10.14434/iujur.v4i1.24499
Nirupama Devanathan, Ann C Kimble-Hill
Epidemiological studies have proposed a link between type II diabetes and cancer via the IGF/insulin signaling pathway, which includes insulin-like peptides (IGF1, IGF2, and insulin), insulin receptors (IR-A, IR-B, IGF1R, and hybrids), and insulin substrate proteins (IRS1-6). In this study, up- and down-regulation of various components in the IGF/insulin signaling pathway are compared to clinical outcomes for cancer patients; the components include diagnosis age, overall survival, tumor invasion and vascularization, and body mass index. It was found that the up-regulation of insulin growth Factor (IGF)/insulin components was associated with overall survival and tumor invasion and vascularization, while the down-regulation of equivalent components was not associated with clinical outcomes assessed in this study. Particularly, the up-regulation of DOK5, IGF2, and IRS2 in colorectal cancer and IGF1R in liver cancer is associated with significantly decreased overall survival. Functional aberrations in either of the two proteins in co-expression pairs were identified for each cancer and correlated with overall survival and diagnosis age. Specific biomarkers proposed in this study will be further analyzed to fine-tune consistent associations that can be translated to reliable prognostic standards for the roles of IGF/insulin signaling pathway modulations that promote cancer.
{"title":"Systematic Survey of the Role of IGF in the Link Between Diabetes and Cancer.","authors":"Nirupama Devanathan, Ann C Kimble-Hill","doi":"10.14434/iujur.v4i1.24499","DOIUrl":"https://doi.org/10.14434/iujur.v4i1.24499","url":null,"abstract":"<p><p>Epidemiological studies have proposed a link between type II diabetes and cancer via the IGF/insulin signaling pathway, which includes insulin-like peptides (IGF1, IGF2, and insulin), insulin receptors (IR-A, IR-B, IGF1R, and hybrids), and insulin substrate proteins (IRS1-6). In this study, up- and down-regulation of various components in the IGF/insulin signaling pathway are compared to clinical outcomes for cancer patients; the components include diagnosis age, overall survival, tumor invasion and vascularization, and body mass index. It was found that the up-regulation of insulin growth Factor (IGF)/insulin components was associated with overall survival and tumor invasion and vascularization, while the down-regulation of equivalent components was not associated with clinical outcomes assessed in this study. Particularly, the up-regulation of DOK5, IGF2, and IRS2 in colorectal cancer and IGF1R in liver cancer is associated with significantly decreased overall survival. Functional aberrations in either of the two proteins in co-expression pairs were identified for each cancer and correlated with overall survival and diagnosis age. Specific biomarkers proposed in this study will be further analyzed to fine-tune consistent associations that can be translated to reliable prognostic standards for the roles of IGF/insulin signaling pathway modulations that promote cancer.</p>","PeriodicalId":92647,"journal":{"name":"Indiana University journal of undergraduate research","volume":"4 1","pages":"17-26"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425955/pdf/nihms-1008167.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37086381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-01-01Epub Date: 2018-12-16DOI: 10.14434/iujur.v4i1.24528
Cameron Peck, Piia Virtanen, Derrick Johnson, Ann C Kimble-Hill
Angiomotins (Amots) are a family of adapter proteins that modulate cellular polarity, differentiation, proliferation, and migration. Amot family members have a characteristic lipid-binding domain, the coiled coil homology (ACCH) domain that selectively targets the protein to membranes, which has been directly linked to its regulatory role in the cell. Several spot blot assays were used to validate the regions of the domain that participate in its membrane association, deformation, and vesicle fusion activity, which indicated the need for a structure to define the mechanism. Therefore, we sought to understand the structure-function relationship of this domain in order to find ways to modulate these signaling pathways. After many failed attempts to crystallize the ACCH domain of each Amot family member for structural analysis, we decided to pursue homologous models that could be refined using small angle x-ray scattering data. Theoretical models were produced using the homology software SWISS-MODEL and threading software I-TASSER and LOMETS, followed by comparison to SAXS data for model selection and refinement. We present a theoretical model of the domain that is driven by alpha helices and short random coil regions. These alpha helical regions form a classic dimer interface followed by two wide spread legs that we predict to be the lipid binding interface.
{"title":"Using the Predicted Structure of the Amot Coiled Coil Homology Domain to Understand Lipid Binding.","authors":"Cameron Peck, Piia Virtanen, Derrick Johnson, Ann C Kimble-Hill","doi":"10.14434/iujur.v4i1.24528","DOIUrl":"10.14434/iujur.v4i1.24528","url":null,"abstract":"<p><p>Angiomotins (Amots) are a family of adapter proteins that modulate cellular polarity, differentiation, proliferation, and migration. Amot family members have a characteristic lipid-binding domain, the coiled coil homology (ACCH) domain that selectively targets the protein to membranes, which has been directly linked to its regulatory role in the cell. Several spot blot assays were used to validate the regions of the domain that participate in its membrane association, deformation, and vesicle fusion activity, which indicated the need for a structure to define the mechanism. Therefore, we sought to understand the structure-function relationship of this domain in order to find ways to modulate these signaling pathways. After many failed attempts to crystallize the ACCH domain of each Amot family member for structural analysis, we decided to pursue homologous models that could be refined using small angle x-ray scattering data. Theoretical models were produced using the homology software SWISS-MODEL and threading software I-TASSER and LOMETS, followed by comparison to SAXS data for model selection and refinement. We present a theoretical model of the domain that is driven by alpha helices and short random coil regions. These alpha helical regions form a classic dimer interface followed by two wide spread legs that we predict to be the lipid binding interface.</p>","PeriodicalId":92647,"journal":{"name":"Indiana University journal of undergraduate research","volume":"4 1","pages":"27-46"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448796/pdf/nihms-1008169.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37291696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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