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  • 标题:Tumors overcome the action of the wasting factor ImpL2 by locally elevating Wnt/Wingless
  • 本地全文:下载
  • 作者:Jiae Lee ; Katelyn G.-L. Ng ; Kenneth M. Dombek
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2021
  • 卷号:118
  • 期号:23
  • 页码:1
  • DOI:10.1073/pnas.2020120118
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Tumors often secrete wasting factors associated with atrophy and the degeneration of host tissues. If tumors were to be affected by the wasting factors, mechanisms allowing tumors to evade the adverse effects of the wasting factors must exist, and impairing such mechanisms may attenuate tumors. We use Drosophila midgut tumor models to show that tumors up-regulate Wingless (Wg) to oppose the growth-impeding effects caused by the wasting factor, ImpL2 (insulin-like growth factor binding protein [IGFBP]-related protein). Growth of Yorkie (Yki)-induced tumors is dependent on Wg while either elimination of ImpL2 or elevation of insulin/insulin-like growth factor signaling in tumors revokes this dependency. Notably, Wg augmentation could be a general mechanism for supporting the growth of tumors with elevated ImpL2 and exploited to attenuate muscle degeneration during wasting. Our study elucidates the mechanism by which tumors negate the action of ImpL2 to uphold their growth during cachexia-like wasting and implies that targeting the Wnt/Wg pathway might be an efficient treatment strategy for cancers with elevated IGFBPs.
  • 关键词:cachexia ; tumor ; Yorkie ; ImpL2 ; Wnt
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