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Article: GLUT5-mediated fructose utilization drives lung cancer growth by stimulating fatty acid synthesis and AMPK/mTORC1 signaling

TitleGLUT5-mediated fructose utilization drives lung cancer growth by stimulating fatty acid synthesis and AMPK/mTORC1 signaling
Authors
Issue Date2020
Citation
JCI Insight, 2020, v. 5, n. 3, article no. e131596 How to Cite?
AbstractLung cancer (LC) is a leading cause of cancer-related deaths worldwide. Its rapid growth requires hyperactive catabolism of principal metabolic fuels. It is unclear whether fructose, an abundant sugar in current diets, is essential for LC. We demonstrated that, under the condition of coexistence of metabolic fuels in the body, fructose was readily used by LC cells in vivo as a glucose alternative via upregulating GLUT5, a major fructose transporter encoded by solute carrier family 2 member 5 (SLC2A5). Metabolomic profiling coupled with isotope tracing demonstrated that incorporated fructose was catabolized to fuel fatty acid synthesis and palmitoleic acid generation in particular to expedite LC growth in vivo. Both in vitro and in vivo supplement of palmitoleic acid could restore impaired LC propagation caused by SLC2A5 deletion. Furthermore, molecular mechanism investigation revealed that GLUT5-mediated fructose utilization was required to suppress AMPK and consequently activate mTORC1 activity to promote LC growth. As such, pharmacological blockade of in vivo fructose utilization using a GLUT5 inhibitor remarkably curtailed LC growth. Together, this study underscores the importance of in vivo fructose utilization mediated by GLUT5 in governing LC growth and highlights a promising strategy to treat LC by targeting GLUT5 to eliminate those fructose-addicted neoplastic cells.
Persistent Identifierhttp://hdl.handle.net/10722/342597
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChen, Wen Lian-
dc.contributor.authorJin, Xing-
dc.contributor.authorWang, Mingsong-
dc.contributor.authorLiu, Dan-
dc.contributor.authorLuo, Qin-
dc.contributor.authorTian, Hechuan-
dc.contributor.authorCai, Lili-
dc.contributor.authorMeng, Lifei-
dc.contributor.authorBi, Rui-
dc.contributor.authorWang, Lei-
dc.contributor.authorXie, Xiao-
dc.contributor.authorYu, Guanzhen-
dc.contributor.authorLi, Lihui-
dc.contributor.authorDong, Changsheng-
dc.contributor.authorCai, Qiliang-
dc.contributor.authorJia, Wei-
dc.contributor.authorWei, Wenyi-
dc.contributor.authorJia, Lijun-
dc.date.accessioned2024-04-17T07:04:55Z-
dc.date.available2024-04-17T07:04:55Z-
dc.date.issued2020-
dc.identifier.citationJCI Insight, 2020, v. 5, n. 3, article no. e131596-
dc.identifier.urihttp://hdl.handle.net/10722/342597-
dc.description.abstractLung cancer (LC) is a leading cause of cancer-related deaths worldwide. Its rapid growth requires hyperactive catabolism of principal metabolic fuels. It is unclear whether fructose, an abundant sugar in current diets, is essential for LC. We demonstrated that, under the condition of coexistence of metabolic fuels in the body, fructose was readily used by LC cells in vivo as a glucose alternative via upregulating GLUT5, a major fructose transporter encoded by solute carrier family 2 member 5 (SLC2A5). Metabolomic profiling coupled with isotope tracing demonstrated that incorporated fructose was catabolized to fuel fatty acid synthesis and palmitoleic acid generation in particular to expedite LC growth in vivo. Both in vitro and in vivo supplement of palmitoleic acid could restore impaired LC propagation caused by SLC2A5 deletion. Furthermore, molecular mechanism investigation revealed that GLUT5-mediated fructose utilization was required to suppress AMPK and consequently activate mTORC1 activity to promote LC growth. As such, pharmacological blockade of in vivo fructose utilization using a GLUT5 inhibitor remarkably curtailed LC growth. Together, this study underscores the importance of in vivo fructose utilization mediated by GLUT5 in governing LC growth and highlights a promising strategy to treat LC by targeting GLUT5 to eliminate those fructose-addicted neoplastic cells.-
dc.languageeng-
dc.relation.ispartofJCI Insight-
dc.titleGLUT5-mediated fructose utilization drives lung cancer growth by stimulating fatty acid synthesis and AMPK/mTORC1 signaling-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1172/jci.insight.131596-
dc.identifier.pmid32051337-
dc.identifier.scopuseid_2-s2.0-85081668706-
dc.identifier.volume5-
dc.identifier.issue3-
dc.identifier.spagearticle no. e131596-
dc.identifier.epagearticle no. e131596-
dc.identifier.eissn2379-3708-
dc.identifier.isiWOS:000514547000008-

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