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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.
Type: article
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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