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A link between lipid metabolism and epithelial-mesenchymal transition generates cells with cancer stem cells characteristics and provides a target for combined drug therapy in colon cancer

AuthorsVargas, Teodoro; Molina, Susana; Moreno-Rubio, Juan; Reglero, Guillermo ; Ramírez de Molina, Ana
Issue Date2015
PublisherCSIC-UAM - Instituto de Investigaciones Biomédicas Alberto Sols (IIBM)
Citation2nd Symposium on Biomedical Research (2015)
AbstractIn recent years there has been a growing interest on the metabolic alterations that fuel tumor growth. In addition to the more studied tumor carbohydrate metabolism, other metabolic pathways involved in malignant progression, such as lipid metabolism, demand further understanding. Here we describe a metabolic acyl-CoA synthetase/stearoyl-CoA desaturase ACSL/SCD network, capable of triggering an epithelialmesenchymal transition (EMT) program that promotes migration and invasion of colon cancer cells without affecting proliferation. Moreover, these cells undergoing EMT are significantly enriched in several well-established markers of colorectal cancer stem cells such as CD44, LGR5 or ALDH1. The mesenchymal phenotype caused upon overexpression of these lipid metabolism enzymes relies on an energetic advantage that is reverted through reactivation of AMPK signaling rescuing the initial epithelial features. Furthermore, stage-II CRC patients with simultaneous overexpression of ACSL/SCD network genes show significantly poorer clinical outcomes. Finally, the combined treatment with chemical inhibitors of ACSL and SCD selectively affects cancer cell viability without affecting normal cells. In addition, this combination is also effective in cancer cells that are resistant to current chemotherapy. Thus, the ACSL/SCD axis might be relevant for colon cancer progression through conferring increased energetic capacity and invasive and migratory properties to cancer cells as well all stem cell properties which are crucial to the development of resistances to current treatments. These new findings, therefore may lead to the development of novel therapeutic approaches for colon cancer.
DescriptionResumen del póster presentado al 2nd Symposium on Biomedical Research: "Advances and perspectives in cancer", celebrado en Madrid el 17 de abril de 2015.-- et al.
Appears in Collections:(CIAL) Comunicaciones congresos
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