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Amy Alvarado

Amy Alvarado poster
STAT2 Signaling Reprograms Lipid Metabolism in Colorectal Cancer

Name Amy Alvarado
Institution Temple University, Lewis Katz School of Medicine 
Research Field Basic Research
Role at Institution Undergraduate Student
Presenter(s) Amy Alvarado

Abstract

STAT2 Signaling Reprograms Lipid Metabolism in Colorectal Cancer

Amy Alvarado1, Nataliya Pryimych1 and Ana M. Gamero1

1Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University 

Our study aims to elucidate molecular mechanisms by which the transcription factor STAT2 promotes colorectal carcinogenesis. Colorectal cancer (CRC) is the third deadliest cancer affecting both men and women. Health disparities in CRC incidence are attributed to a myriad of factors that range from genetics to unhealthy lifestyle and poor access to medical care in communities of low socio-economic status. Therefore, increased knowledge on the signaling networks involved in disease initiation and progression are imperative to combat CRC. We have collected data employing different animal models of CRC that reproducibly show STAT2 contributes to tumor growth. Transcriptomic profiling of colon tumor xenografts revealed a subset of genes involved in cholesterol metabolism to be downregulated in the absence of STAT2. We identified LIPG as the top hit gene that is involved in lipid uptake and recently shown to promote the growth and metastasis of breast cancer. Lipidomic analysis of tumor xenografts showed that STAT2 reprogrammed the composition of tumor lipids. To determine a relationship between STAT2 and LIPG, we found that treatment with pharmacological inhibitors of LIPG decreased viability of tumor cells expressing STAT2 with mild effect in STAT2 deficient cells. We also found that a deficiency in STAT2 impaired lipid uptake as measured by the accumulation of lipid droplets following incubation with phosphatidylcholine-oleic acid, a LIPG substrate. Altogether, our preliminary findings indicate a novel uncharacterized function of STAT2 that promotes CRC by rewiring lipid metabolism. 

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