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Lysosomal trafficking mediated by Arl8b and BORC promotes invasion of cancer cells that survive radiation
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| Title: | Lysosomal trafficking mediated by Arl8b and BORC promotes invasion of cancer cells that survive radiation |
| Authors: | Wu, Ping-Hsiu Browse this author | | Onodera, Yasuhito Browse this author →KAKEN DB | | Giaccia, Amato J. Browse this author | | Quynh-Thu Le Browse this author | | Shimizu, Shinichi Browse this author →KAKEN DB | | Shirato, Hiroki Browse this author →KAKEN DB | | Nam, Jin-Min Browse this author →KAKEN DB |
| Issue Date: | 27-Oct-2020 |
| Publisher: | Nature Research |
| Journal Title: | Communications biology |
| Volume: | 3 |
| Issue: | 1 |
| Start Page: | 620 |
| Publisher DOI: | 10.1038/s42003-020-01339-9 |
| Abstract: | Enhanced invasiveness, a critical determinant of metastasis and poor prognosis, has been observed in cancer cells that survive cancer therapy, including radiotherapy. Here, we show that invasiveness in radiation-surviving cancer cells is associated with alterations in lysosomal exocytosis caused by the enhanced activation of Arl8b, a small GTPase that regulates lysosomal trafficking. The binding of Arl8b with its effector, SKIP, is increased after radiation through regulation of BORC-subunits. Knockdown of Arl8b or BORC-subunits decreases lysosomal exocytosis and the invasiveness of radiation-surviving cells. Notably, high expression of ARL8B and BORC-subunit genes is significantly correlated with poor prognosis in breast cancer patients. Sp1, an ATM-regulated transcription factor, is found to increase BORC-subunit genes expression after radiation. In vivo experiments show that ablation of Arl8b decreases IR-induced invasive tumor growth and distant metastasis. These findings suggest that BORC-Arl8b-mediated lysosomal trafficking is a target for improving radiotherapy by inhibiting invasive tumor growth and metastasis. |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/80649 |
| Appears in Collections: | 国際連携研究教育局 : GI-CoRE (Global Institution for Collaborative Research and Education : GI-CoRE) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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