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Oncogenic Pathways and Loss of the Rab11 GTPase Synergize To Alter Metabolism in .
Citation | “Oncogenic Pathways And Loss Of The Rab11 Gtpase Synergize To Alter Metabolism In .”. Genetics, pp. 1227-1239. . |
Author | Yingchao Nie, Shiyan Yu, Qi Li, Niraj K Nirala, Alla Amcheslavsky, Yvonne J K Edwards, Patrick W Shum, Zhong Jiang, Wei Wang, Biliang Zhang, Nan Gao, Tony Ip |
Keywords | Drosophila, ImpL2, Rab11, Ras, colon cancer, intestine, Metabolism |
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 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 to regulate these cancer-related phenotypes. |
Year of Publication |
2019
|
Journal |
Genetics
|
Volume |
212
|
Issue |
4
|
Number of Pages |
1227-1239
|
Date Published |
12/2019
|
ISSN Number |
1943-2631
|
DOI |
10.1534/genetics.119.302137
|
Alternate Journal |
Genetics
|
PMID |
31213502
|
PMCID |
PMC6707446
|
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