학술논문
Oncogenic Pathways and Loss of the Rab11 GTPase Synergize To Alter Metabolism in Drosophila .
Document Type
Academic Journal
Author
Nie Y; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605.; Yu S; Department of Biological Sciences, Rutgers University, Newark, New Jersey 07102.; Li Q; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605.; Nirala NK; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605.; Amcheslavsky A; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605.; Edwards YJK; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605.; Shum PW; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605.; Jiang Z; Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01605.; Wang W; Guangzhou RiboBio Co., Ltd., Guangzhou 510663, China.; Zhang B; Guangzhou RiboBio Co., Ltd., Guangzhou 510663, China.; Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.; Gao N; Department of Biological Sciences, Rutgers University, Newark, New Jersey 07102.; Ip YT; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605 Tony.Ip@umassmed.edu.
Source
Publisher: Oxford University Press Country of Publication: United States NLM ID: 0374636 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1943-2631 (Electronic) Linking ISSN: 00166731 NLM ISO Abbreviation: Genetics Subsets: MEDLINE
Subject
Language
English
Abstract
Colorectal cancer is a complex disease driven by well-established mutations such as APC and other yet to be identified pathways. The GTPase Rab11 regulates endosomal protein trafficking, and previously we showed that loss of Rab11 caused intestinal inflammation and hyperplasia in mice and flies. To test the idea that loss of Rab11 may promote cancer progression, we have analyzed archival human patient tissues and observed that 51 out of 70 colon cancer tissues had lower Rab11 protein staining. By using the Drosophila midgut model, we have found that loss of Rab11 can lead to three changes that may relate to cancer progression. First is the disruption of enterocyte polarity based on staining of the FERM domain protein Coracle. Second is an increased proliferation due to an increased expression of the JAK-STAT pathway ligand Upd3. Third is an increased expression of ImpL2, which is an IGFBP7 homolog and can suppress metabolism. Furthermore, loss of Rab11 can act synergistically with the oncoprotein Ras V12 to regulate these cancer-related phenotypes.
(Copyright © 2019 by the Genetics Society of America.)
(Copyright © 2019 by the Genetics Society of America.)