Oncogenic Pathways and Loss of the Rab11 GTPase Synergize To Alter Metabolism in Drosophila
Program in Molecular Medicine; Department of Pathology
Biochemical Phenomena, Metabolism, and Nutrition | Cancer Biology | Cellular and Molecular Physiology | Digestive System | Digestive System Diseases | Genetic Phenomena | Genetics and Genomics | Neoplasms | Pathological Conditions, Signs and Symptoms
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.
Drosophila, ImpL2, Rab11, Ras, colon cancer, intestine, metabolism
DOI of Published Version
Genetics. 2019 Jun 18. pii: genetics.302137.2019. doi: 10.1534/genetics.119.302137. [Epub ahead of print] Link to article on publisher's site
Nie, Yingchao; Yu, Shiyan; Li, Qi; Nirala, Niraj K.; Amcheslavsky, Alla; Edwards, Yvonne J. K.; Shum, Patrick W.; Jiang, Zhong; Wang, Wei; Zhang, Biliang; Gao, Nan; and Ip, Y. Tony, "Oncogenic Pathways and Loss of the Rab11 GTPase Synergize To Alter Metabolism in Drosophila" (2019). Open Access Articles. 3881.