Metastasis still accounts for 90% of all cancer-related death cases. An increase of cellular mobility and invasive traits of cancer cells mark two crucial prerequisites of metastasis. Recent studies highlight the involvement of the endolysosomal cation channel TRPML1 in cell migration. Our results identified a widely antimigratory effect upon loss of TRPML1 function in a panel of cell lines in vitro and reduced dissemination in vivo. As mode-of-action, we established TRPML1 as a crucial regulator of cytosolic calcium levels, actin polymerization, and intracellular trafficking of two promigratory proteins: E-cadherin and beta 1-integrin. Interestingly, KO of TRPML1 differentially interferes with the recycling process of E-cadherin and beta 1-integrin in a cell line-dependant manner, while resulting in the same phenotype of decreased migratory and adhesive capacities in vitro. Additionally, we observed a coherence between reduction of E-cadherin levels at membrane site and phosphorylation of NF-kappa B in a beta-catenin/p38-mediated manner. As a result, an E-cadherin/NF-kappa B feedback loop is generated, regulating E-cadherin expression on a transcriptional level. Consequently, our findings highlight the role of TRPML1 as a regulator in migratory processes and suggest the ion channel as a suitable target for the inhibition of migration and invasion.
机构:
Fudan Univ, Minhang Hosp, Shanghai, Peoples R China
Fudan Univ, Int Colab Med Epigenet & Metab, Minist Sci & Technol, Inst Biomed Sci,Shanghai Key Lab Med Epigenet, Shanghai, Peoples R ChinaFudan Univ, Minhang Hosp, Shanghai, Peoples R China
Wang, Jie
Yan, Hai-Bo
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Fudan Univ, Minhang Hosp, Shanghai, Peoples R China
Fudan Univ, Int Colab Med Epigenet & Metab, Minist Sci & Technol, Inst Biomed Sci,Shanghai Key Lab Med Epigenet, Shanghai, Peoples R ChinaFudan Univ, Minhang Hosp, Shanghai, Peoples R China
Yan, Hai-Bo
Zhang, Qian
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机构:
Fudan Univ, Minhang Hosp, Shanghai, Peoples R China
Fudan Univ, Int Colab Med Epigenet & Metab, Minist Sci & Technol, Inst Biomed Sci,Shanghai Key Lab Med Epigenet, Shanghai, Peoples R ChinaFudan Univ, Minhang Hosp, Shanghai, Peoples R China
Zhang, Qian
Liu, Wei-Yan
论文数: 0引用数: 0
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机构:
Fudan Univ, Minhang Hosp, Shanghai, Peoples R China
Fudan Univ, Int Colab Med Epigenet & Metab, Minist Sci & Technol, Inst Biomed Sci,Shanghai Key Lab Med Epigenet, Shanghai, Peoples R ChinaFudan Univ, Minhang Hosp, Shanghai, Peoples R China
Liu, Wei-Yan
Jiang, Ying-Hua
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机构:
Fudan Univ, Minhang Hosp, Shanghai, Peoples R China
Fudan Univ, Int Colab Med Epigenet & Metab, Minist Sci & Technol, Inst Biomed Sci,Shanghai Key Lab Med Epigenet, Shanghai, Peoples R ChinaFudan Univ, Minhang Hosp, Shanghai, Peoples R China
Jiang, Ying-Hua
Peng, Gang
论文数: 0引用数: 0
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机构:
Fudan Univ, Inst Brain Sci, Shanghai, Peoples R ChinaFudan Univ, Minhang Hosp, Shanghai, Peoples R China
Peng, Gang
Wu, Fei-Zhen
论文数: 0引用数: 0
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机构:
Fudan Univ, Sch Basic Med Sci, Dept Syst Biol Med, Shanghai, Peoples R ChinaFudan Univ, Minhang Hosp, Shanghai, Peoples R China
Wu, Fei-Zhen
Liu, Xin
论文数: 0引用数: 0
h-index: 0
机构:
Shanghai Univ Tradit Chinese Med, Shanghai Municipal Hosp Tradit Chinese Med, Dept Cent Lab Med, Shanghai, Peoples R ChinaFudan Univ, Minhang Hosp, Shanghai, Peoples R China
Liu, Xin
Yang, Peng-Yuan
论文数: 0引用数: 0
h-index: 0
机构:
Fudan Univ, Minhang Hosp, Shanghai, Peoples R China
Fudan Univ, Int Colab Med Epigenet & Metab, Minist Sci & Technol, Inst Biomed Sci,Shanghai Key Lab Med Epigenet, Shanghai, Peoples R China
Fudan Univ, Sch Basic Med Sci, Dept Syst Biol Med, Shanghai, Peoples R China
Fudan Univ, Dept Chem, Shanghai, Peoples R ChinaFudan Univ, Minhang Hosp, Shanghai, Peoples R China
Yang, Peng-Yuan
Liu, Feng
论文数: 0引用数: 0
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机构:
Fudan Univ, Minhang Hosp, Shanghai, Peoples R China
Fudan Univ, Int Colab Med Epigenet & Metab, Minist Sci & Technol, Inst Biomed Sci,Shanghai Key Lab Med Epigenet, Shanghai, Peoples R China
Fudan Univ, Sch Basic Med Sci, Dept Syst Biol Med, Shanghai, Peoples R ChinaFudan Univ, Minhang Hosp, Shanghai, Peoples R China
机构:
Peoples Hosp Laiwu, Dept Gen Surg, Laiwu 271100, Shandong, Peoples R ChinaPeoples Hosp Laiwu, Dept Gen Surg, Laiwu 271100, Shandong, Peoples R China
Zhao, Wei
Lu, Mingshu
论文数: 0引用数: 0
h-index: 0
机构:
Peoples Hosp Laiwu, Dept Gen Surg, Laiwu 271100, Shandong, Peoples R ChinaPeoples Hosp Laiwu, Dept Gen Surg, Laiwu 271100, Shandong, Peoples R China
Lu, Mingshu
Zhang, Qiwen
论文数: 0引用数: 0
h-index: 0
机构:
Peoples Hosp Laiwu, Dept Gen Surg, Laiwu 271100, Shandong, Peoples R ChinaPeoples Hosp Laiwu, Dept Gen Surg, Laiwu 271100, Shandong, Peoples R China
机构:
Kaohsiung Vet Gen Hosp, Dept Otorhinolaryngol Head & Neck Surg, Kaohsiung, Taiwan
Natl Def Med Ctr, Grad Inst Aerosp & Undersea Med, Taipei, Taiwan
Tajen Univ, Dept Pharm, Pingtung, TaiwanKaohsiung Vet Gen Hosp, Dept Otorhinolaryngol Head & Neck Surg, Kaohsiung, Taiwan
Kang, Bor-Hwang
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机构:
Shu, Chih-Wen
Chao, Jian-Kang
论文数: 0引用数: 0
h-index: 0
机构:
Kaohsiung Vet Gen Hosp, Dept Psychiat, Pingtung Branch, Pingtung, TaiwanKaohsiung Vet Gen Hosp, Dept Otorhinolaryngol Head & Neck Surg, Kaohsiung, Taiwan
Chao, Jian-Kang
Lee, Cheng-Hsin
论文数: 0引用数: 0
h-index: 0
机构:
Kaohsiung Vet Gen Hosp, Dept Med Educ & Res, Kaohsiung, TaiwanKaohsiung Vet Gen Hosp, Dept Otorhinolaryngol Head & Neck Surg, Kaohsiung, Taiwan
Lee, Cheng-Hsin
Fu, Ting-Ying
论文数: 0引用数: 0
h-index: 0
机构:
Kaohsiung Vet Gen Hosp, Dept Pathol & Lab Med, Kaohsiung, TaiwanKaohsiung Vet Gen Hosp, Dept Otorhinolaryngol Head & Neck Surg, Kaohsiung, Taiwan
Fu, Ting-Ying
Liou, Huei-Han
论文数: 0引用数: 0
h-index: 0
机构:
Kaohsiung Vet Gen Hosp, Dept Med Educ & Res, Kaohsiung, TaiwanKaohsiung Vet Gen Hosp, Dept Otorhinolaryngol Head & Neck Surg, Kaohsiung, Taiwan
Liou, Huei-Han
Ger, Luo-Ping
论文数: 0引用数: 0
h-index: 0
机构:
Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung, Taiwan
Kaohsiung Vet Gen Hosp, Dept Med Educ & Res, Kaohsiung, TaiwanKaohsiung Vet Gen Hosp, Dept Otorhinolaryngol Head & Neck Surg, Kaohsiung, Taiwan
Ger, Luo-Ping
Liu, Pei-Feng
论文数: 0引用数: 0
h-index: 0
机构:
Kaohsiung Vet Gen Hosp, Dept Med Educ & Res, Kaohsiung, Taiwan
Shu Zen Jr Coll Med & Management, Dept Oral Hyg, Kaohsiung, TaiwanKaohsiung Vet Gen Hosp, Dept Otorhinolaryngol Head & Neck Surg, Kaohsiung, Taiwan
机构:
China Med Univ, Affiliated Hosp 1, Dept Pathol, 77 Puhe Rd, Shenyang 110001, Liaoning, Peoples R China
China Med Univ, Coll Basic Med Sci, 77 Puhe Rd, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Affiliated Hosp 1, Dept Pathol, 77 Puhe Rd, Shenyang 110001, Liaoning, Peoples R China
Zhang, Xiupeng
Jiang, Guiyang
论文数: 0引用数: 0
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机构:
China Med Univ, Affiliated Hosp 1, Dept Pathol, 77 Puhe Rd, Shenyang 110001, Liaoning, Peoples R China
China Med Univ, Coll Basic Med Sci, 77 Puhe Rd, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Affiliated Hosp 1, Dept Pathol, 77 Puhe Rd, Shenyang 110001, Liaoning, Peoples R China
Jiang, Guiyang
Wu, Jingjing
论文数: 0引用数: 0
h-index: 0
机构:
China Med Univ, Affiliated Hosp 1, Dept Pathol, 77 Puhe Rd, Shenyang 110001, Liaoning, Peoples R China
China Med Univ, Coll Basic Med Sci, 77 Puhe Rd, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Affiliated Hosp 1, Dept Pathol, 77 Puhe Rd, Shenyang 110001, Liaoning, Peoples R China
Wu, Jingjing
Zhou, Haijing
论文数: 0引用数: 0
h-index: 0
机构:
China Med Univ, Affiliated Hosp 1, Dept Pathol, 77 Puhe Rd, Shenyang 110001, Liaoning, Peoples R China
China Med Univ, Coll Basic Med Sci, 77 Puhe Rd, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Affiliated Hosp 1, Dept Pathol, 77 Puhe Rd, Shenyang 110001, Liaoning, Peoples R China
Zhou, Haijing
Zhang, Yong
论文数: 0引用数: 0
h-index: 0
机构:
China Med Univ, Dept Pathol, Canc Hosp, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Affiliated Hosp 1, Dept Pathol, 77 Puhe Rd, Shenyang 110001, Liaoning, Peoples R China
Zhang, Yong
Miao, Yuan
论文数: 0引用数: 0
h-index: 0
机构:
China Med Univ, Affiliated Hosp 1, Dept Pathol, 77 Puhe Rd, Shenyang 110001, Liaoning, Peoples R China
China Med Univ, Coll Basic Med Sci, 77 Puhe Rd, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Affiliated Hosp 1, Dept Pathol, 77 Puhe Rd, Shenyang 110001, Liaoning, Peoples R China
Miao, Yuan
Feng, Yangyang
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h-index: 0
机构:
China Med Univ, Affiliated Hosp 1, Dept Pathol, 77 Puhe Rd, Shenyang 110001, Liaoning, Peoples R China
China Med Univ, Coll Basic Med Sci, 77 Puhe Rd, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Affiliated Hosp 1, Dept Pathol, 77 Puhe Rd, Shenyang 110001, Liaoning, Peoples R China
Feng, Yangyang
Yu, Juanhan
论文数: 0引用数: 0
h-index: 0
机构:
China Med Univ, Affiliated Hosp 1, Dept Pathol, 77 Puhe Rd, Shenyang 110001, Liaoning, Peoples R China
China Med Univ, Coll Basic Med Sci, 77 Puhe Rd, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Affiliated Hosp 1, Dept Pathol, 77 Puhe Rd, Shenyang 110001, Liaoning, Peoples R China
机构:
Univ Tokyo, Inst Med Sci, Mol Pathol Lab, Tokyo, Japan
Jichi Med Univ, Dept Integrat Pathol, Shimotsukeshi, Tochigi 3290498, JapanUniv Tokyo, Inst Med Sci, Mol Pathol Lab, Tokyo, Japan
Matsubara, Daisuke
Kishaba, Yuka
论文数: 0引用数: 0
h-index: 0
机构:
Jichi Med Univ, Dept Integrat Pathol, Shimotsukeshi, Tochigi 3290498, JapanUniv Tokyo, Inst Med Sci, Mol Pathol Lab, Tokyo, Japan
Kishaba, Yuka
Yoshimoto, Taichiro
论文数: 0引用数: 0
h-index: 0
机构:
Jichi Med Univ, Dept Integrat Pathol, Shimotsukeshi, Tochigi 3290498, JapanUniv Tokyo, Inst Med Sci, Mol Pathol Lab, Tokyo, Japan
Yoshimoto, Taichiro
Sakuma, Yuji
论文数: 0引用数: 0
h-index: 0
机构:
Jichi Med Univ, Dept Integrat Pathol, Shimotsukeshi, Tochigi 3290498, JapanUniv Tokyo, Inst Med Sci, Mol Pathol Lab, Tokyo, Japan
Sakuma, Yuji
Sakatani, Takashi
论文数: 0引用数: 0
h-index: 0
机构:
Jichi Med Univ, Dept Integrat Pathol, Shimotsukeshi, Tochigi 3290498, JapanUniv Tokyo, Inst Med Sci, Mol Pathol Lab, Tokyo, Japan
Sakatani, Takashi
Tamura, Tomoko
论文数: 0引用数: 0
h-index: 0
机构:
Jichi Med Univ, Dept Integrat Pathol, Shimotsukeshi, Tochigi 3290498, JapanUniv Tokyo, Inst Med Sci, Mol Pathol Lab, Tokyo, Japan
Tamura, Tomoko
Endo, Shunsuke
论文数: 0引用数: 0
h-index: 0
机构:
Jichi Med Univ, Div Gen Thorac Surg, Shimotsukeshi, Tochigi 3290498, JapanUniv Tokyo, Inst Med Sci, Mol Pathol Lab, Tokyo, Japan
Endo, Shunsuke
Sugiyama, Yukihiko
论文数: 0引用数: 0
h-index: 0
机构:
Jichi Med Univ, Div Pulm Med, Shimotsukeshi, Tochigi 3290498, JapanUniv Tokyo, Inst Med Sci, Mol Pathol Lab, Tokyo, Japan
Sugiyama, Yukihiko
Murakami, Yoshinori
论文数: 0引用数: 0
h-index: 0
机构:
Univ Tokyo, Inst Med Sci, Mol Pathol Lab, Tokyo, JapanUniv Tokyo, Inst Med Sci, Mol Pathol Lab, Tokyo, Japan
Murakami, Yoshinori
Niki, Toshiro
论文数: 0引用数: 0
h-index: 0
机构:
Jichi Med Univ, Dept Integrat Pathol, Shimotsukeshi, Tochigi 3290498, JapanUniv Tokyo, Inst Med Sci, Mol Pathol Lab, Tokyo, Japan
机构:
302 Hosp PLA, Dept Hepatobiliary Surg, Beijing 100039, Peoples R ChinaFourth Mil Med Univ, Xijing Hosp, Dept Hepatobiliary Surg, Xian 710032, Shaanxi, Peoples R China
Yu, Ling-Xiang
Zhou, Liang
论文数: 0引用数: 0
h-index: 0
机构:
Fourth Mil Med Univ, Xijing Hosp, Dept Hepatobiliary Surg, Xian 710032, Shaanxi, Peoples R ChinaFourth Mil Med Univ, Xijing Hosp, Dept Hepatobiliary Surg, Xian 710032, Shaanxi, Peoples R China
Zhou, Liang
Li, Mo
论文数: 0引用数: 0
h-index: 0
机构:
Fourth Mil Med Univ, Xijing Hosp, Dept Orthopaed, Xian 710032, Shaanxi, Peoples R ChinaFourth Mil Med Univ, Xijing Hosp, Dept Hepatobiliary Surg, Xian 710032, Shaanxi, Peoples R China
Li, Mo
Li, Zhi-Wei
论文数: 0引用数: 0
h-index: 0
机构:
302 Hosp PLA, Dept Hepatobiliary Surg, Beijing 100039, Peoples R ChinaFourth Mil Med Univ, Xijing Hosp, Dept Hepatobiliary Surg, Xian 710032, Shaanxi, Peoples R China
Li, Zhi-Wei
Wang, De-Sheng
论文数: 0引用数: 0
h-index: 0
机构:
Fourth Mil Med Univ, Xijing Hosp, Dept Hepatobiliary Surg, Xian 710032, Shaanxi, Peoples R ChinaFourth Mil Med Univ, Xijing Hosp, Dept Hepatobiliary Surg, Xian 710032, Shaanxi, Peoples R China
Wang, De-Sheng
Zhang, Shao-Geng
论文数: 0引用数: 0
h-index: 0
机构:
302 Hosp PLA, Dept Hepatobiliary Surg, Beijing 100039, Peoples R ChinaFourth Mil Med Univ, Xijing Hosp, Dept Hepatobiliary Surg, Xian 710032, Shaanxi, Peoples R China