Loss of Rab5 drives non-autonomous cell proliferation through TNF and Ras signaling in Drosophila |
| |
Authors: | Kyoko Takino Shizue Ohsawa Tatsushi Igaki |
| |
Affiliation: | 1. Laboratory of Genetics, Graduate School of Biostudies, Kyoto University, Yoshida-Konoecho-cho, Sakyo-ku, Kyoto 606-8501, Japan;2. Division of Genetics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan;3. PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan |
| |
Abstract: | Deregulation of the endocytic machinery has been implicated in human cancers. However, the mechanism by which endocytic defects drive cancer development remains to be clarified. Here, we find through a genetic screen in Drosophila that loss of Rab5, a protein required for early endocytic trafficking, drives non-autonomous cell proliferation in imaginal epithelium. Our genetic data indicate that dysfunction of Rab5 leads to cell-autonomous accumulation of Eiger (a TNF homolog) and EGF receptor (EGFR), which causes activation of downstream JNK and Ras signaling, respectively. JNK signaling and its downstream component Cdc42 cooperate with Ras signaling to induce upregulation of a secreted growth factor Upd (an IL-6 homolog) through inactivation of the Hippo pathway. Such non-autonomous tissue growth triggered by Rab5 defect could contribute to epithelial homeostasis as well as cancer development within heterogeneous tumor microenvironment. |
| |
Keywords: | Tissue growth regulation Cell&ndash cell interaction Tumorigenesis Rab5 Drosophila |
本文献已被 ScienceDirect 等数据库收录! |
|