Endolysosomal TRPML1 channel regulates cancer cell migration by altering intracellular trafficking of E-cadherin and β 1-integrin

被引:4
|
作者
Frey, Nadine [1 ]
Ouologuem, Lina [1 ]
Blenninger, Julia [1 ,2 ]
Siow, Wei-Xiong [1 ]
Thorn-Seshold, Julia
Stoeckl, Jan [3 ]
Abrahamian, Carla [4 ]
Froehlich, Thomas [3 ]
Vollmar, Angelika M. [1 ]
Grimm, Christian [4 ]
Bartel, Karin [1 ]
机构
[1] Ludwig Maximilians Univ Munchen, Dept Pharm, Pharmaceut Biol, Munich, Germany
[2] Ludwig Maximilians Univ Munchen, Dept Pharm, Munich, Germany
[3] Ludwig Maximilians Univ Munchen, Gene Ctr, Lab Funct Genome Anal, Munich, Germany
[4] Ludwig Maximilians Univ Munchen, Walther Straub Inst Pharmacol & Toxicol, Munich, Germany
关键词
NF-KAPPA-B; MESENCHYMAL TRANSITION; ION-CHANNEL; METASTASIS; INTEGRINS; INVASION; ACTIVATION; EXPRESSION; SUPPRESSES; EXOCYTOSIS;
D O I
10.1016/j.jbc.2023.105581
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页数:16
相关论文
共 50 条
  • [41] Enhancement of E-cadherin expression and processing and driving of cancer cell metastasis by ARID1A deficiency
    Wang, Jie
    Yan, Hai-Bo
    Zhang, Qian
    Liu, Wei-Yan
    Jiang, Ying-Hua
    Peng, Gang
    Wu, Fei-Zhen
    Liu, Xin
    Yang, Peng-Yuan
    Liu, Feng
    ONCOGENE, 2021, 40 (36) : 5468 - 5481
  • [42] Overexpression of integrin-linked kinase (ILK) promotes glioma cell invasion and migration and down-regulates E-cadherin via the NF-κB pathway
    Feng Liang
    Shuqin Zhang
    Bing Wang
    Jianwu Qiu
    Yunjie Wang
    Journal of Molecular Histology, 2014, 45 : 141 - 151
  • [43] Chloride intracellular channel 1 regulates migration and invasion in gastric cancer by triggering the ROS-mediated p38 MAPK signaling pathway
    Zhao, Wei
    Lu, Mingshu
    Zhang, Qiwen
    MOLECULAR MEDICINE REPORTS, 2015, 12 (06) : 8041 - 8047
  • [44] HER2 Upregulates ATF4 to Promote Cell Migration via Activation of ZEB1 and Downregulation of E-Cadherin
    Zeng, Peng
    Sun, Shengnan
    Li, Rui
    Xiao, Zhi-Xiong
    Chen, Hu
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2019, 20 (09)
  • [45] HSPD1 repressed E-cadherin expression to promote cell invasion and migration for poor prognosis in oral squamous cell carcinoma
    Kang, Bor-Hwang
    Shu, Chih-Wen
    Chao, Jian-Kang
    Lee, Cheng-Hsin
    Fu, Ting-Ying
    Liou, Huei-Han
    Ger, Luo-Ping
    Liu, Pei-Feng
    SCIENTIFIC REPORTS, 2019, 9 (1)
  • [46] MicroRNA-200a inhibits CD133/1+ovarian cancer stem cells migration and invasion by targeting E-cadherin repressor ZEB2
    Wu, Qiuhua
    Guo, Rongjiao
    Lin, Min
    Zhou, Bing
    Wang, Yifeng
    GYNECOLOGIC ONCOLOGY, 2011, 122 (01) : 149 - 154
  • [47] Zinc finger protein 668 suppresses non-small cell lung cancer invasion and migration by downregulating Snail and upregulating E-cadherin and zonula occludens-1
    Zhang, Xiupeng
    Jiang, Guiyang
    Wu, Jingjing
    Zhou, Haijing
    Zhang, Yong
    Miao, Yuan
    Feng, Yangyang
    Yu, Juanhan
    ONCOLOGY LETTERS, 2018, 15 (03) : 3806 - 3813
  • [48] Immunohistochemical analysis of the expression of E-cadherin and ZEB1 in non-small cell lung cancer
    Matsubara, Daisuke
    Kishaba, Yuka
    Yoshimoto, Taichiro
    Sakuma, Yuji
    Sakatani, Takashi
    Tamura, Tomoko
    Endo, Shunsuke
    Sugiyama, Yukihiko
    Murakami, Yoshinori
    Niki, Toshiro
    PATHOLOGY INTERNATIONAL, 2014, 64 (11) : 560 - 568
  • [49] The Notch1/cyclooxygenase-2/Snail/E-cadherin pathway is associated with hypoxia-induced hepatocellular carcinoma cell invasion and migration
    Yu, Ling-Xiang
    Zhou, Liang
    Li, Mo
    Li, Zhi-Wei
    Wang, De-Sheng
    Zhang, Shao-Geng
    ONCOLOGY REPORTS, 2013, 29 (01) : 362 - 370
  • [50] MORF4L1 suppresses cell proliferation, migration and invasion by increasing p21 and E-cadherin expression in nasopharyngeal carcinoma
    Sang, Yi
    Zhang, Ruhua
    Sun, Longhua
    Chen, Kaddie Kwok
    Li, Si-Wei
    Xiong, Longxin
    Peng, Yongjian
    Zeng, Lei
    Huang, Guofu
    ONCOLOGY LETTERS, 2019, 17 (01) : 294 - 302