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Ral GTPase promotes metastasis of pancreatic ductal adenocarcinoma via elevation of TGF-β1 production

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Pubmed体系：

收录情况： ◇ 自然指数

作者：
Cao Mingxin[1,2,3,4] ; Li Xinming[5] ; Trinh Duc-Anh[1] ; Yoshimachi Shingo[1,6] ; Goto Kota[1] ; Sakata Natsumi[1] ; Ishida Masaharu[6] ; Ohtsuka Hideo[6] ; Unno Michiaki[6] ; Wang Yuxia[5] ; Shirakawa Ryutaro[1] ; Horiuchi Hisanori[1,2,*1] ;
机构： [1]Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan [2]Department of Oral Cancer Therapeutics, Graduate School of Dentistry, Tohoku University, Sendai, Miyagi, Japan [3]State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China [4]School and Hospital of Stomatology, Tianjin Medical University, Tianjin, China [5]Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin Stomatological Hospital, The Affiliated Stomatological Hospital of Nankai University, Tianjin, China [6]Department of Surgery, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, Japan
出处：
DOI： 10.1016/j.jbc.2023.104754
ISSN：

关键词： RalGAP Ral GTPase TGF-β1 pancreatic ductal adenocarcinoma metastasis

摘要：
Pancreatic ductal adenocarcinoma (PDAC), caused by activating mutations in K-Ras, is an aggressive malignancy due to its early invasion and metastasis. Ral GTPases are activated downstream of Ras and play a crucial role in the development and progression of PDAC. However, the underlying mechanisms remain unclear. In this study, we investigated the mechanism of Ral-induced invasion and metastasis of PDAC cells using RalGAPβ-deficient PDAC cells with highly activated Ral GTPases. Array analysis and enzyme-linked immunosorbent assays revealed increased expression and secretion of TGF-β1 in RalGAPβ-deficient PDAC cells compared to control cells. Blockade of TGF-β1 signaling suppressed RalGAPβ deficiency-enhanced migration and invasion in vitro and metastasis in vivo to levels similar to controls. Phosphorylation of c-Jun N-terminal kinase (JNK), a repressor of TGF-β1 expression, was decreased by RalGAPβ deficiency. These results indicate that Ral contributes to invasion and metastasis of PDAC cells by elevating autocrine TGF-β1 signaling at least in part by decreasing JNK activity.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

基金：
This study was supported by Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research JP16H05148 (R.S.) and JP16K08574 (H.H.), Tianjin Health Commission Science and Technology Talent Cultivation Project KJ20089 (Y.W.), and Tianjin Key Medical Discipline (Specialty) Construction Project.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学
最新[2023]版：
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学
第一作者：
第一作者机构： [1]Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan [2]Department of Oral Cancer Therapeutics, Graduate School of Dentistry, Tohoku University, Sendai, Miyagi, Japan [3]State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China [4]School and Hospital of Stomatology, Tianjin Medical University, Tianjin, China
通讯作者：
通讯机构： [1]Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan [2]Department of Oral Cancer Therapeutics, Graduate School of Dentistry, Tohoku University, Sendai, Miyagi, Japan [*1]Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
推荐引用方式(GB/T 7714)：
Cao Mingxin,Li Xinming,Trinh Duc-Anh,et al.Ral GTPase promotes metastasis of pancreatic ductal adenocarcinoma via elevation of TGF-β1 production[J].The Journal of biological chemistry.2023,104754.doi:10.1016/j.jbc.2023.104754.
APA：
Cao Mingxin,Li Xinming,Trinh Duc-Anh,Yoshimachi Shingo,Goto Kota...&Horiuchi Hisanori.(2023).Ral GTPase promotes metastasis of pancreatic ductal adenocarcinoma via elevation of TGF-β1 production.The Journal of biological chemistry,,
MLA：
Cao Mingxin,et al."Ral GTPase promotes metastasis of pancreatic ductal adenocarcinoma via elevation of TGF-β1 production".The Journal of biological chemistry .(2023):104754

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